Journal articles: 'GPC1'

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Mucientes, A., E. Herranz, P. Lois, F. J. Blanco, L. Abasolo, L. Rodriguez Rodriguez, J. R. Lamas, and B. Fernandez. "AB0077 CONTRIBUTION OF NOTUM TO THE DEVELOPMENT OF OSTEOARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1338.1–1339. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4569.

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Background:Osteoarthritis (OA) is a degenerative disease characterized by altered homeostasis of joint cartilage and bone, the functionality of which relies on chondrocytes and osteoblasts, that leads to the formation of a defective extracellular matrix (ECM). The ECM plays an essential role in bone biology as it provides the structure of cartilage which serves as a template for bone formation. Collagen X, main component of the ECM, has been described by our group as down-regulated in OA [1]. Our data also points to an important role of the Wnt pathway in OA [1,2]. Furthermore, Wnt proteins have been reported to inhibit chondrogenesis [3], and the Wnt pathway and its modulators have gained attention [4]. Glypicans (GPC1 to GPC6) and NOTUM, among others, have been identified as modulators of this pathway [5,6]. Notably, due to its highly specific inhibition of the Wnt pathway, NOTUM has been proposed as a therapeutic target in conditions with a high activity of the Wnt pathway is involved, such as OA [7].Objectives:We hypothesize that modulators of the Wnt pathway are involved in the development of OA. The aim of this study is to evaluate the presence of Glypicans and NOTUM in the serum of OA patients and healthy individuals in order to determine whether significant differences exist and could clarify their likely involvement in OA.Methods:Peripheral blood samples were obtained from OA patients during routine rheumatologist hospital visits. OA diagnosis was established according to the ACR criteria. Samples from healthy individuals were obtained from the local Blood Bank. In both cases, blood samples were centrifugated (2000g, 15 minutes, 10°C) and serum was obtained.Quantitative ELISA assays for GPC1-6 and NOTUM were carried out using commercial kits (Human GPC1 ELISA Kit, #E-EL-H1710, Elabscience; Human GPC2 ELISA Kit, #E-EL-H1711, Elabscience; Human GPC3 ELISA Kit, #E-EL-H1712, Elabscience; Human GPC4 ELISA Kit, #E-EL-H1713, Elabscience; Human GPC5 ELISA Kit, #ELH-GPC5, RayBiotech; Human GPC6 ELISA Kit, #CSB-EL009708HU, Cusabio; Human Protein NOTUM homolog ELISA Kit, #EK3787, Sab Biotech) and measured in a plate reader (Heales MB-580,Shenzhen Heales Technology Development Co. Ltd.). Protein concentration in serum was calculated using GraphPad Prism 7 software. Differences between samples were analysed with Mann-Withney U test. Significance level set wasp<0.05.Results:Serum from 40 OA patients and 40 healthy donors were included in the study. There were no differences between groups (Table 1).Table 1.Cohort descriptionControl group (n=40)OA group (n=40)Age66,82±5,7569,59±11,24Women (%)32 (80%)30 (75%)Out of 7 proteins analyzed, only NOTUM showed a significant difference between healthy and OA groups (MedianOA=0.4451ng/mL, MedianCONTROL=0.8263ng/mL,p=0.0013). Besides, GPC4 showed an approaching formal significance (MedianOA=0.1254ng/mL, MedianCONTROL=0.1596ng/mL,p=0.0767). The rest of Glypicans analyzed showed no significance differences between groups (GPC1, MedianOA=0.1346ng/mL, MedianCONTROL=0.1190ng/mL,p=0.2379; GPC2, MedianOA=2.593ng/mL, MedianCONTROL=2.955ng/mL,p=0.7489; GPC3, MedianOA=2.024ng/mL, MedianCONTROL=1.422ng/mL,p=0.3574; GPC5, MedianOA=3.663ng/mL, MedianCONTROL=5.529ng/mL,p=0.8829; GPC6, MedianOA=0.3922ng/mL, MedianCONTROL=0.3558ng/mL,p=0.3212).Conclusion:Our results suggest that low levels of NOTUM may contribute to the development of OA. The lack of this inhibitor promotes the activation of the Wnt pathway, high activity of which has been related with OA.References:[1]Lamas JRet al.Ann Rheum Dis, 2010. 69(10):1880-5.[2]Tornero-Esteban Pet al. PLoS One, 2015. 10(9): p. e0137170.[3]Dayet al. Dev Cell. 2005. 8(5):739-50.[4]Monteagudo S and Lories RJ. Nat Rev Rheumatol, 2017. 13(11): p. 670-681.[6]Li Net al. Trends Cancer. 2018 Nov;4(11):741-754.[7]De Robertis Met al. Oncotarget, 2015. 6(38): p. 41237-57.[8]Nusse R. Nature, 2015. 519(7542): p. 163-4.Disclosure of Interests:Arkaitz Mucientes: None declared, Eva Herranz: None declared, Pia Lois: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer, Lydia Abasolo: None declared, Luis Rodriguez Rodriguez: None declared, José Ramón Lamas: None declared, Benjamin Fernandez: None declared

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Wang, Shiqing, Zhenzhen Wu, Minyu Zhou, and Wangjun Liao. "Effect of GPC1 on epithelial-to-mesenchymal transition and stemness and interaction with ITGB1 in gastric cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e15580-e15580. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e15580.

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e15580 Background: Gastric cancer is the fourth frequently diagnosed cancer worldwide and tumor metastasis plays an important role in its poor prognosis. EMT, which occurs during embryonic development and carcinoma progression, contributes to metastasis and regulates stemness. GPC1, a member of the heparan sulfate proteoglycans family, is overexpressed in many types of cancer, and associates with metastasis and tumor progression. However, it is unknown that the functions of GPC1 and its underlying mechanism in gastric cancer. Methods: Immunohistochemistry analysis was performed in 245 GC tissues to explore the relationship between GPC1 and tumor metastasis. Transwell migration and wound-healing assay were conducted to evaluate the effects of GPC1 on migration and invasiveness. Epithelial marker and mesenchymal markers expression in GC cells were detected by Western blot and immunofluorescence. GPC1 expression induced by TGF-β was detected by Western Blot. After GPC1 was knock downed, the metastatic effect and EMT markers induced by TGF-β were detected. Co-Immunoprecipitation was used to detect the interaction between ITGB1 and GPC1. Results: The expression of GPC1 was higher in GC tissues than in adjacent normal tissues and associated with poor prognosis. Knocking down GPC1 suppressed EMT and stemness which reduced metastasis in vivo and vitro by inhibiting Erk1/2 MAPK and FAK/Akt pathways. TGF-β stimulation significantly upregulated the expression of GPC1 whereas knocking down of GPC1 reversed TGF-β-mediated EMT and stemness. Moreover, we found that knocking down GPC1 could downregulate ITGB1 which was known to promote EMT in gastric cancer. Overexpression of ITGB1 counteracted the influence of knocking down GPC1 on EMT and stemness. Furthermore, GPC1 formed a complex with ITGB1, which indicated that the ability of GPC1 to stimulate EMT is ITGB1-dependent. Conclusions: We conclude that GPC1, through its interaction with ITGB1, plays an important role in regulating TGF-β-mediated EMT and stemness, and could be a potential future therapeutic target to prevent progression of gastric cancer.

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Lu, Fei, Shuran Chen, Weijun Shi, Xu Su, Huazhang Wu, and Mulin Liu. "GPC1 promotes the growth and migration of colorectal cancer cells through regulating the TGF-β1/SMAD2 signaling pathway." PLOS ONE 17, no. 6 (June 7, 2022): e0269094. http://dx.doi.org/10.1371/journal.pone.0269094.

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In this study, we analyzed GPC family genes in colorectal cancer (CRC) and the possible mechanism of action of GPC1 in CRC. CRC patient data were extracted from The Cancer Genome Atlas, and the prognostic significance of GPC1 expression and its association with clinicopathological features were identified by Kolmogorov–Smirnov test. CRC patients with high GPC1 expression had poor overall survival compared with patients with low GPC1 expression. In vitro experiments demonstrated that knockdown of GPC1 significantly inhibited the proliferation and migration and promoted cell apoptosis in CRC cell lines. Gene Ontology analysis of differential genes indicated that GPC1 may influence the TGF-β1 signaling pathway. Additional experiments revealed that silencing GPC1 suppressed the levels of TGF-β1 and p-SMAD2 but increased the expression of SMAD2. Taken together, these findings suggest that GPC1 may function as a tumor promoter in CRC cells through promoting TGF-β signaling pathway. Our results also indicate that GPC1 may serve as a critical effector in CRC progression and a new potential target for CRC therapy.

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Qiao, Dianhua, Xinhai Yang, Kristy Meyer, and Andreas Friedl. "Glypican-1 Regulates Anaphase Promoting Complex/Cyclosome Substrates and Cell Cycle Progression in Endothelial Cells." Molecular Biology of the Cell 19, no. 7 (July 2008): 2789–801. http://dx.doi.org/10.1091/mbc.e07-10-1025.

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Glypican-1 (GPC1), a member of the mammalian glypican family of heparan sulfate proteoglycans, is highly expressed in glioma blood vessel endothelial cells (ECs). In this study, we investigated the role of GPC1 in EC replication by manipulating GPC1 expression in cultured mouse brain ECs. Moderate GPC1 overexpression stimulates EC growth, but proliferation is significantly suppressed when GPC1 expression is either knocked down or the molecule is highly overexpressed. Flow cytometric and biochemical analyses show that high or low expression of GPC1 causes cell cycle arrest at mitosis or the G2 phase of the cell cycle, accompanied by endoreduplication and consequently polyploidization. We further show that GPC1 inhibits the anaphase-promoting complex/cyclosome (APC/C)–mediated degradation of mitotic cyclins and securin. High levels of GPC1 induce metaphase arrest and centrosome overproduction, alterations that are mimicked by overexpression of cyclin B1 and cyclin A, respectively. These observations suggest that GPC1 regulates EC cell cycle progression at least partially by modulating APC/C-mediated degradation of mitotic cyclins and securin.

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Qiao, Dianhua, Kristy Meyer, and Andreas Friedl. "Glypican 1 Stimulates S Phase Entry and DNA Replication in Human Glioma Cells and Normal Astrocytes." Molecular and Cellular Biology 33, no. 22 (September 9, 2013): 4408–21. http://dx.doi.org/10.1128/mcb.00238-13.

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Malignant gliomas are highly lethal neoplasms with limited treatment options. We previously found that the heparan sulfate proteoglycan glypican 1 (GPC1) is universally and highly expressed in human gliomas. In this study, we investigated the biological activity of GPC1 expression in both human glioma cells and normal astrocytesin vitro. Expression of GPC1 inactivates the G1/S checkpoint and strongly stimulates DNA replication. Constitutive expression of GPC1 causes DNA rereplication and DNA damage, suggesting a mutagenic activity for GPC1. GPC1 expression leads to a significant downregulation of the tumor suppressors pRb, Cip/Kip cyclin-dependent kinase inhibitors (CKIs), and CDH1, and upregulation of the pro-oncogenic proteins cyclin E, cyclin-dependent kinase 2 (CDK2), Skp2, and Cdt1. These GPC1-induced changes are accompanied by a significant reduction in all types of D cyclins, which is independent of serum supplementation. It is likely that GPC1 stimulates the so-called Skp2 autoinduction loop, independent of cyclin D-CDK4/6. Knockdown of Skp2, CDK2, or cyclin E, three key elements within the network modulated by GPC1, results in a reduction of the S phase and aneuploid fractions, implying a functional role for these regulators in GPC1-induced S phase entry and DNA rereplication. In addition, a significant activation of both the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways by GPC1 is seen in normal human astrocytes even in the presence of growth factor supplement. Both pathways are constitutively activated in human gliomas. The surprising magnitude and the mitogenic and mutagenic nature of the effect exerted by GPC1 on the cell cycle imply that GPC1 may play an important role in both glioma tumorigenesis and growth.

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Liu, Ying, Hui Ren, Mu-qing Yang, and Ji-yu Li. "GPC1 Is Associated with Poor Prognosis and Treg Infiltration in Colon Adenocarcinoma." Computational and Mathematical Methods in Medicine 2022 (September 14, 2022): 1–15. http://dx.doi.org/10.1155/2022/8209700.

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Glypican-1 (GPC1) is a glycosylated protein recognized as a promising biomarker for cancer. Nonetheless, there have been few systematic studies on GPC1 in colon adenocarcinoma (COAD). We conducted bioinformatic analysis based on The Cancer Genome Atlas (TCGA) and used clinical samples to verify that GPC1 is overexpressed in colon adenocarcinoma. Kaplan-Meier analysis showed that higher GPC1 expression was associated with poor overall survival (OS). The Cox regression model further showed that GPC1 expression is an independent negative prognostic factor for COAD. Gene set enrichment analysis demonstrated that multiple oncogenic signaling pathways were differentially enriched in GPC1 high- versus low-expressing COAD tumors, including DNA methylation, G2/M damage checkpoint, and telomere dysfunction. We observed a positive correlation between GPC1 expression and immune cell infiltration, such as regulatory T cells (Tregs), macrophages, and mast cells, and immunohistochemistry of 50 COAD tissues revealed that GPC1 expression was positively associated with Treg enrichment. Our results provide a promising candidate gene to predict the prognosis of COAD and new insights into tumor immunity. Further research is required to validate these results.

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Schlaepfer Sales, Caroline B., Vanessa S. N. Guimarães, Ludmila F. Valverde, Rosane B. Dias, Raíza D. Freitas, Leonardo de Oliveira Siquara da Rocha, Malu Coelho de Miranda, et al. "Glypican-1, -3, -5 (GPC1, GPC3, GPC5) and Hedgehog Pathway Expression in Oral Squamous Cell Carcinoma." Applied Immunohistochemistry & Molecular Morphology 29, no. 5 (January 27, 2021): 345–51. http://dx.doi.org/10.1097/pai.0000000000000907.

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Whipple, Chery A., Arthur D. Lander, and Murray Korc. "Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis." Scientific World JOURNAL 8 (2008): 1250–53. http://dx.doi.org/10.1100/tsw.2008.152.

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The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cellsin vivoand markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell–derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer.

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Khurana, Satish, Chacko Joseph, Lia Margamuljana, Shannon Buckley, Sarah Scouteden, and Catherine M. Verfaillie. "Tissue Factor Pathway Inhibitor Increases Hematopoietic Stem Cell Homing and Engraftment by Glypican-3 Mediated Inhibition of CD26 Activity." Blood 118, no. 21 (November 18, 2011): 725. http://dx.doi.org/10.1182/blood.v118.21.725.725.

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Abstract Abstract 725 Directional migration is an important factor that determines homing of transplanted hematopoietic stem cells (HSC). The SDF-1α-CXCR4 axis is one of the most important determinants of this process. CD26, expressed on various cell types, leads to proteolytic cleavage of SDF-1α, which leads to the inactivation of its chemokine activity. We identified tissue factor pathway inhibitor (TFPI) as an inhibitor of CD26. Culture of murine bone marrow derived c-kit+Lin−Sca-1+ (KLS) cells or human umbilical cord blood derived Lin−CD34+ cells with TFPI significantly inhibited CD26 activity, which resulted in significantly increased migration towards SDF-1α. Moreover, TFPI treatment of murine KLS cells led to significant improvement in homing following intravenous injection and long-term reconstitution upon transplantation in competitive repopulation assays. We found that the effects of TFPI were mediated by the heparan sulphate proteoglycan, Glypican-3 (Gpc3). TFPI directly bound Gpc3; TFPI did not affect CD26 activity, migration or homing of Gpc3−/− KLS cells, but affected Gpc1−/− KLS cells similar to the wild type. Finally, KLS cells from Gpc3−/− but not Gpc1−/− mice homed significantly less following IV injection. Hence, we present a novel molecule that can be used in an HSC specific manner to enhance HSC migration, homing and engraftment. Disclosures: No relevant conflicts of interest to declare.

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Qiu, Wenli, Huifeng Zhang, Xiao Chen, Lina Song, Wenjing Cui, Shuai Ren, Yajie Wang, et al. "A GPC1-targeted and gemcitabine-loaded biocompatible nanoplatform for pancreatic cancer multimodal imaging and therapy." Nanomedicine 14, no. 17 (September 2019): 2339–53. http://dx.doi.org/10.2217/nnm-2019-0063.

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Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer.

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Colin-Pierre, Charlie, Valérie Untereiner, Ganesh D. Sockalingum, Laurent Ramont, and Stéphane Brézillon. "Investigation of Glypican-4 and -6 by Infrared Spectral Imaging during the Hair Growth Cycle." International Journal of Molecular Sciences 24, no. 5 (February 21, 2023): 4291. http://dx.doi.org/10.3390/ijms24054291.

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The expression of glypicans in different hair follicle (HF) compartments is still poorly understood. Heparan sulfate proteoglycans (HSPGs) distribution in HF is classically investigated by conventional histology, biochemical analysis, and immunohistochemistry. Our previous study proposed a novel approach to assess hair histology and glypican-1 (GPC1) distribution changes in the HF at different phases of the hair growth cycle using infrared spectral imaging (IRSI). We show in the present manuscript for the first time complementary data on the distribution of glypican-4 (GPC4) and glypican-6 (GPC6) in HF at different phases of the hair growth cycle using IR imaging. Findings were supported by Western blot assays focusing on the GPC4 and GPC6 expression in HFs. Like all proteoglycan features, the glypicans are characterized by a core protein to which sulfated and/or unsulfated glycosaminoglycan (GAG) chains are covalently linked. Our study demonstrates the capacity of IRSI to identify the different HF tissue structures and to highlight protein, proteoglycan (PG), GAG, and sulfated GAG distribution in these structures. The comparison between anagen, catagen, and telogen phases shows the qualitative and/or quantitative evolution of GAGs, as supported by Western blot. Thus, in one analysis, IRSI can simultaneously reveal the location of proteins, PGs, GAGs and sulfated GAGs in HFs in a chemical and label-free manner. From a dermatological point of view, IRSI may constitute a promising technique to study alopecia.

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Kaushik, Nikita. "A Possible Role of Pulegone against Glypican-1 for the Treatment of Alzheimer’s Disease through In-Silico Approach." International Journal for Research in Applied Science and Engineering Technology 9, no. VI (June 30, 2021): 4000–4007. http://dx.doi.org/10.22214/ijraset.2021.35932.

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Alzheimer’s disease (AD) dementia is a type of neurodegenerative disease, refers to a distinct arrival and certainly functional and mental decline which is linked with age which eventually leads to death. This current study was to demonstrate the role of pulegone against Glypican-1 for the treatment of Alzheimer’s disease through an in-silico approach. Methods: All the information and studies were gleaned from molecular docking. With the use of docking software, Docking was implemented between the target protein GPC1 (PDB ID: 4YWT) and the entire ligands. We preferred GPC1 (PDB ID: 4YWT) as a target protein and several natural compounds such as Rosmarinic acid, Allo ocimene, and Pulegone as ligands. When the preparation of protein is done, in PyRx software we introduced the entire ligand for the process of virtual screening. As reported by the result of PyRx and Lipinski’s Rule of Five, the finest compound against GPC1 with its smallest amount of binding energy was Pulegone. Results: For the procedure of molecular docking between the receptor protein GPC1 (PDB ID: 4YWT) and Pulegone a software called AutoDock Vina was used. The outcome showed 9 poses with distinct binding energy, RMSD LB (Root means square deviation Lower Bound), RMSD UB (Root mean square deviation Upper Bound). Through PyMol (an open-access tool for the visualization of the molecule), the interaction amidst Pulegone and GPC1 can be visualized. Conclusion: The merely compound which can restrain the activity of GPC1 (PDB ID: 4YWT) was Pulegone, based on the in-silico approach. Therefore in the advanced studies, Pulegone can be a capable medicine acquired from natural sources for dealing with Alzheimer’s disease.

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Papiewska-Pająk, Izabela, Damian Krzyżanowski, Maria Katela, Romain Rivet, Sylwia Michlewska, Patrycja Przygodzka, M. Anna Kowalska, and Stéphane Brézillon. "Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing Snail." Cells 9, no. 7 (June 30, 2020): 1585. http://dx.doi.org/10.3390/cells9071585.

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The transcription factor Snail triggers epithelial-to-mesenchymal transition (EMT), endowing cancer cells with invasive properties during tumor progression. Extracellular vesicles (EVs) released from cancer cells at various stages of cancer progression are known to influence the tumor pre-metastatic niche and metastatic potential. The aim of this study was to analyze the effect of Snail on murine colon adenocarcinoma cells (MC38 line) and on the characteristics of their EVs. Stable clones of Snail-overexpressing MC38 cells were investigated in vitro versus Mock cells. Increased expression of matrix metalloproteinase MMP-14 and augmented activity of MMP-9 and -14 were observed in Snail-MC38 cells. There was no change in the transcriptomic profile of proteoglycans in Snail-MC38 cells; however, the protein level of Glypican-1 (GPC1) was enhanced in EVs released from those cells. Our finding that GPC1 protein level was enhanced in EVs released from MC38 cells that overexpressed Snail and were in an early EMT stage might explain the specificity of the GPC1 biomarker in colon cancer diagnosis. Further, our data suggest that Snail, by changing the level of GPC1 on EVs released by colon cancer cells, may affect the generation of a distant premetastatic niche and metastatic organotropism in colon adenocarcinoma.

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Huang, Mi, Yingying Ma, Xiaoyan Gao, Xinyang Li, Quan Ding, Chuxin Liu, Xiaopan Liu, Hang Zhang, and Naibo Yang. "Combining Fluorescent Cell Sorting and Single B Cell Amplification to Screen the Monoclonal Antibody Gene against Human Glypican-1 in Pancreatic Cancer." Journal of Oncology 2021 (September 3, 2021): 1–8. http://dx.doi.org/10.1155/2021/5646589.

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In this report, one novel method has been developed to screen the monoclonal antibody against human pancreatic cancer biomarker glypican-1 (GPC1) through the combination of fluorescent cell sorting and single B cell amplification. GPC1-positive B cells were sorted out from the peripheral blood mononuclear cells (PBMCs) by fluorescent cell sorting after the GPC1 immunization to the New Zealand white rabbit. Then, total RNA was extracted and reversely transcribed into cDNA, which was used as the template, and the variable region sequences of both heavy and light chains were amplified from the same B cell. Next, their recombinant antibody was expressed and purified from the human 293T cell after the antibody gene amplification and expression vector construction. The enzyme-linked immunosorbent assay (ELISA) and flow cytometry assays were used to determine the antibody affinity. The antibody named GPC-12 that we screened and obtained was proven to have natural heavy-light chain pairing information, and it was highly specific to the GPC1 antigen, and the affinity could reach 1 × 10−7 M. Overall, an effective and novel method has been successfully developed to screen the antibody by combining the fluorescent cell sorting and single-cell amplifying technologies, which was proved to be workable in our setting.

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Dwivedi, Prem P., Randall H. Grose, Jorge Filmus, Charles S. T. Hii, Cory J. Xian, Peter J. Anderson, and Barry C. Powell. "Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3." Bone 55, no. 2 (August 2013): 367–76. http://dx.doi.org/10.1016/j.bone.2013.04.013.

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Buscail, Etienne, Catherine Alix-Panabières, Pascaline Quincy, Thomas Cauvin, Alexandre Chauvet, Olivier Degrandi, Charline Caumont, et al. "High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery." Cancers 11, no. 11 (October 26, 2019): 1656. http://dx.doi.org/10.3390/cancers11111656.

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Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.

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Busato, Davide, Monica Mossenta, Michele Dal Bo, Paolo Macor, and Giuseppe Toffoli. "The Proteoglycan Glypican-1 as a Possible Candidate for Innovative Targeted Therapeutic Strategies for Pancreatic Ductal Adenocarcinoma." International Journal of Molecular Sciences 23, no. 18 (September 7, 2022): 10279. http://dx.doi.org/10.3390/ijms231810279.

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Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers, with a 5-year survival rate of 7% and 80% of patients diagnosed with advanced or metastatic malignancies. Despite recent advances in diagnostic testing, surgical techniques, and systemic therapies, there remain limited options for the effective treatment of PDAC. There is an urgent need to develop targeted therapies that are able to differentiate between cancerous and non-cancerous cells to reduce side effects and better inhibit tumor growth. Antibody-targeted strategies are a potentially effective option for introducing innovative therapies. Antibody-based immunotherapies and antibody-conjugated nanoparticle-based targeted therapies with antibodies targeting specific tumor-associated antigens (TAA) can be proposed. In this context, glypican-1 (GPC1), which is highly expressed in PDAC and not expressed or expressed at very low levels in non-malignant lesions and healthy pancreatic tissues, is a useful TAA that can be achieved by a specific antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy. In this review, we describe the main clinical features of PDAC. We propose the proteoglycan GPC1 as a useful TAA for PDAC-targeted therapies. We also provide a digression on the main developed approaches of antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy, which can be used to target GPC1.

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Estevão, Bianca Martins, Edson José Comparetti, Nathalia Cristina Rissi, and Valtencir Zucolotto. "Anti-GPC1-modified mesoporous silica nanoparticles as nanocarriers for combination therapy and targeting of PANC-1 cells." Materials Advances 2, no. 15 (2021): 5224–35. http://dx.doi.org/10.1039/d1ma00225b.

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We present a novel therapeutic nanoplatform based on mesoporous silica nanoparticles encapsulating ferulic acid/gemcitabine and functionalized with anti-GPC1 antibodies to target human pancreatic cancer (PANC-1) cells.

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Grillo, Paulina Karin, Balázs Győrffy, and Martin Götte. "Prognostic impact of the glypican family of heparan sulfate proteoglycans on the survival of breast cancer patients." Journal of Cancer Research and Clinical Oncology 147, no. 7 (March 19, 2021): 1937–55. http://dx.doi.org/10.1007/s00432-021-03597-4.

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Abstract Purpose Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancer patients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancer patients. Methods We used a public database including both gene expression data and survival information for 3951 breast cancer patients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines. Results We found that high GPC3 levels were associated with a better prognosis in overall breast cancer patients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival. Conclusion Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancer patients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.

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de Boer, T. J. L., M. E. Huber, E. A. Magnier, P. M. Onaka, K. C. Chambers, C. C. Lin, H. Gao, J. Fairlamb, and R. J. Wainscoat. "Characterizing Crosstalk within the Pan-STARRS GPC1 Camera." Publications of the Astronomical Society of the Pacific 134, no. 1032 (February 1, 2022): 024501. http://dx.doi.org/10.1088/1538-3873/ac4de3.

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Abstract Using data from a year-long dedicated campaign to observe bright stars, we study the crosstalk channels present in the GPC1 camera. By analyzing these data, we construct a data set that checks source stars on almost every CCD of every chip within the camera against all possible crosstalk destinations. We use a clustering algorithm to find potential crosstalk occurrences, and then also check all possible combinations (driven by the hardware layout) by eye. This results in a total of 640 rules, with a flux attenuation factor ranging from 2.5 × 102 for the bright end to 2.5 × 104 at the faint end. The average value of m cross–m src ≈ −10.25 corresponds to an attenuating factor of 1.25 × 104, which produces crosstalk ghosts with an average signal-to-noise ratio of 0.64 ± 0.1 on the bright images. We find no evidence of crosstalk signals between CCDs not connected in the hardware setup. The distribution of attenuation factors is also found to be dependent on crosstalk movement. A clear dependence on cell column offsets is found, consistent with the idea that the source star charge is progressively attenuated during the traversal of cell readout lines. While we can see the trends, the uncertainties on aperture magnitude measurements are large at this stage.

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Tanaka, Mariko, Shumpei Ishikawa, Tetsuo Ushiku, Teppei Morikawa, Takayuki Isagawa, Makoto Yamagishi, Hiroyuki Yamamoto, et al. "EVI1 modulates oncogenic role of GPC1 in pancreatic carcinogenesis." Oncotarget 8, no. 59 (September 1, 2017): 99552–66. http://dx.doi.org/10.18632/oncotarget.20601.

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Filmus, Jorge. "The function of glypicans in the mammalian embryo." American Journal of Physiology-Cell Physiology 322, no. 4 (April 1, 2022): C694—C698. http://dx.doi.org/10.1152/ajpcell.00045.2022.

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Glypicans are proteoglycans that are bound to the outer surface of the plasma membrane by a glycosylphosphatidylinositol anchor. The mammalian genome contains six members of the glypican family ( GPC1 to GPC6). Although the degree of sequence homology within the family is rather low, the three-dimensional structure of these proteoglycans is highly conserved. Glypicans are predominantly expressed during embryonic development. Genetic and biochemical studies have shown that glypicans can stimulate or inhibit the signaling pathways triggered by Wnts, hedgehogs, fibroblast growth factors, and bone morphogenetic proteins. The study of mutant mouse strains demonstrated that glypicans have important functions in the developmental morphogenesis of various organs. In addition, a role of glypicans in synapsis formation has been established. Notably, glypican loss-of-function mutations are the cause of three human inherited syndromes. Recent analysis of glypican compound mutant mice has demonstrated that members of this protein family display redundant functions during embryonic development.

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Lorente-Gea, Laura, Beatriz García, Carla Martín, Helena Ordiales, Olivia García-Suárez, Kelvin M. Piña-Batista, Jesús Merayo-Lloves, Luís M. Quirós, and Iván Fernández-Vega. "Heparan Sulfate Proteoglycans Undergo Differential Expression Alterations in Alzheimer Disease Brains." Journal of Neuropathology & Experimental Neurology 79, no. 5 (February 24, 2020): 474–83. http://dx.doi.org/10.1093/jnen/nlaa016.

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Abstract Previous studies have reported that heparan sulfate proteoglycans (HSPGs) promote amyloid-beta peptide and tau fibrillization in Alzheimer disease (AD) and provide resistance against proteolytic breakdown. We compared the expression levels of 17 HSPG core proteins in 18 AD cases and 6 controls. RT-PCR was used to analyze transcription levels. Immunohistochemistry was performed to localize HSPGs in the brain tissue. We detected expression of all HSPG genes investigated. SDC1, GPC3, and CD44v3 showed the lowest levels of expression, while SDC3 and GPC1 showed the highest. Remarkably, SDC4 and SRGN were overexpressed in most of the areas analyzed. Immunohistochemistry revealed the presence of both SDC4 and SRGN mostly associated with tau and amyloid-β pathology throughout the AD brains. In conclusion, in view of the involvement of HSPGs in AD pathology, especially SDC4 and SRGN, there would seem to be a relationship between the regulation of core protein expression and the pathological features suggesting HSPGs are potential inducers of the disease.

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Kong, Chunli, Lianghui Cheng, Guido Krenning, Jolien Fledderus, Bart J. de Haan, Marthe T. C. Walvoort, and Paul de Vos. "Human Milk Oligosaccharides Mediate the Crosstalk Between Intestinal Epithelial Caco-2 Cells and Lactobacillus PlantarumWCFS1in an In Vitro Model with Intestinal Peristaltic Shear Force." Journal of Nutrition 150, no. 8 (June 15, 2020): 2077–88. http://dx.doi.org/10.1093/jn/nxaa162.

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ABSTRACT Background The intestinal epithelial cells, food molecules, and gut microbiota are continuously exposed to intestinal peristaltic shear force. Shear force may impact the crosstalk of human milk oligosaccharides (hMOs) with commensal bacteria and intestinal epithelial cells. Objectives We investigated how hMOs combined with intestinal peristaltic shear force impact intestinal epithelial cells and crosstalk with a commensal bacterium. Methods We applied the Ibidi system to mimic intestinal peristaltic shear force. Caco-2 cells were exposed to a shear force (5 dynes/cm2) for 3 d, and then stimulated with the hMOs, 2′-fucosyllactose (2′-FL), 3-FL, and lacto-N-triose II (LNT2). In separate experiments, Lactobacillus plantarumWCFS1 adhesion to Caco-2 cells was studied with the same hMOs and shear force. Effects were tested on gene expression of glycocalyx-related molecules (glypican 1 [GPC1], hyaluronan synthase 1 [HAS1], HAS2, HAS3, exostosin glycosyltransferase 1 [EXT1], EXT2), defensin β-1 (DEFB1), and tight junction (tight junction protein 1 [TJP1], claudin 3 [CLDN3]) in Caco-2 cells. Protein expression of tight junctions was also quantified. Results Shear force dramatically decreased gene expression of the main enzymes for making glycosaminoglycan side chains (HAS3 by 43.3% and EXT1 by 68.7%) (P <0.01), but did not affect GPC1 which is the gene responsible for the synthesis of glypican 1 which is a major protein backbone of glycocalyx. Expression of DEFB1, TJP1, and CLDN3 genes was decreased 60.0–94.9% by shear force (P <0.001). The presence of L. plantarumWCFS1 increased GPC1, HAS2, HAS3, and ZO-1 expression by 1.78- to 3.34-fold (P <0.05). Under shear force, all hMOs significantly stimulated DEFB1 and ZO-1, whereas only 3-FL and LNT2 enhanced L. plantarumWCFS1 adhesion by 1.85- to 1.90-fold (P <0.01). Conclusions 3-FL and LNT2 support the crosstalk between the commensal bacterium L. plantarumWCFS1 and Caco-2 intestinal epithelial cells, and shear force can increase the modulating effects of hMOs.

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Girerd, Sandrine, Lucie Tosca, Olivier Herault, Christine Vignon, Denis Biard, Fatima Dkhissi, Clémentine Bouneau, et al. "Superoxide Dismutase 2 (Sod2) Expression Is Highly Decreased In Chronic Myeloid Leukemia (CML): Contribution To Genetic Instability In Bcr-Abl-Expressing Leukemic Cells." Blood 122, no. 21 (November 15, 2013): 3980. http://dx.doi.org/10.1182/blood.v122.21.3980.3980.

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Abstract A increased oxidative stress is one of the hallmarks of chronic myeloid leukemia (CML). Manganese Superoxide dismutase 2 (SOD2) is a key scavenger enzyme against reactive oxygen species (ROS) in eukaryotic cells, playing a crucial role in antioxidant defense but its potential implication in the CML pathophysiology is not determined. We have analyzed the expression of SOD2 at the RNA level in a large cohort of CML patients (n=49) compared to a cohort of controls with non-malignant hyperleucocytosis (n= 19). This analysis showed a major decrease of SOD2 mRNA, inversely correlated with leucocytosis (p< 0.0001) and with Sokal Score, high-risk patients showing a lower expression of SOD2 (p= 0.019). To determine the effects of the silencing of SOD2 gene in an experimental CML model, we analyzed SOD2 expression in the human UT7 cell line expressing either native or BCR-ABL carrying T315I mutation. SOD2 protein levels in BCR-ABL expressing cells were similar to parental UT7 cells, suggesting that BCR-ABL has no direct effect on SOD2 expression. We have then silenced SOD2 expression in UT7 cells as well as UT7-BCR-ABL cells. Interestingly, the expression of H2O2 levels measured with flow cytometry was not changed after SOD2 inhibition, suggesting activation of compensatory anti-oxidant pathways. A global analysis of 27 anti-oxidant gene expression showed a reduction of PRDX2 only in BCR-ABL-expressing cells. To analyze same cells at the genomic level, we have performed CGH arrays in SOD2 silenced UT7, UT7-BCR-ABL and UT7-T315I cells as compared to their counterparts expressing SOD2. These experiments showed a major genetic instability with deletions and duplications in several chromosomal loci only in native or T315I-mutated BCR-ABL expressing cells silenced for SOD2. The 13q31.3-q34 locus, containing GPC5 and GPC6 genes, was found to be duplicated in non-mutated BCR-ABL cells deficient in SOD2 expression. GPC5 and GPC5 belong to the Glypican family, which are cell surface heparan sulfate proteoglycans anchored to the cell membrane via glycosyl-phosphatidyl-inositol-structures. The expression of several GPC is increased in some malignancies, including glioma, pancreatic carcinoma, breast cancer (GPC1), hepatocellular carcinoma (GPC3) and rhabdomyosarcoma (GPC5). Furthermore, the 13.q31.3 region, duplicated in BCR-ABL-expressing cells upon SOD2 deletion, contains the polycistronic mir-17-92 cluster (mir-17, mir-18a, mir19a, mir-20a, mir-19b1, mir-92a1), which is highly increased in CML CD34+ cells. Interestingly, the inhibition of SOD2 expression did not lead to the same genomic modifications detected by CGH arrays; the duplication of the 13q31.3 and 13q31.3q24 regions was not found in UT7 BCR-ABL cells harboring the T315I mutation. T315I cells silenced for SOD2 expression exhibited multiple abnormalities among which a large deletion of the 20q11.21 region which encodes the defensin gene family (DEFB115, DEFB116, DEFB118, DEFB119, DEFB121, DEFB122, DEFB123, DEFB124; REM1, DUSP15). Beta-defensins are antimicrobial peptides, which are part of the innate immunity against pathogens. The loss of beta-defensin 1 gene has already been reported in solid tumors. In conclusion, we demonstrate in a large cohort of CML patients, a major decrease of SOD2 expression, involved in antioxidant defense. We further show for the first time a link between loss of SOD2 expression and genetic instability in BCR-ABL expressing cells as demonstrated by CGH arrays. Genetic consequences of reduced SOD2 expression in CML should be further analyzed in prospective studies as patients with low SOD2 expression could be more prone to develop a mutator phenotype under TKI therapies. Disclosures: Guilhot: Novartis, BMS, Ariad, Pfizer: Honoraria. Turhan:Bristol Myers Squibb, Novartis: Consultancy, Honoraria.

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Asundi, Vinod K., Bonnie F. Keister, and David J. Carey. "Organization, 5′-flanking sequence and promoter activity of the rat GPC1 gene." Gene 206, no. 2 (January 1998): 255–61. http://dx.doi.org/10.1016/s0378-1119(97)00594-5.

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Perrot, G., C. Colin-Pierre, L. Ramont, I. Proult, C. Garbar, V. Bardey, C. Jeanmaire, et al. "Decreased expression of GPC1 in human skin keratinocytes and epidermis during ageing." Experimental Gerontology 126 (October 2019): 110693. http://dx.doi.org/10.1016/j.exger.2019.110693.

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Bai, Mei-Rong, Wei-Bo Niu, Ying Zhou, Yi-Ming Gong, Yan-Jiao Lu, Xian-Xian Yu, Zhi-Liang Wei, et al. "Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility." Aging 12, no. 8 (April 21, 2020): 7163–82. http://dx.doi.org/10.18632/aging.103067.

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Smith, Katherine. "GPC1 genetic risk further links Hedgehog signalling with pathogenesis of biliary atresia." Nature Reviews Gastroenterology & Hepatology 10, no. 3 (February 5, 2013): 127. http://dx.doi.org/10.1038/nrgastro.2013.20.

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Rzhevskiy, Alexey S., Sajad Razavi Bazaz, Lin Ding, Alina Kapitannikova, Nima Sayyadi, Douglas Campbell, Bradley Walsh, David Gillatt, Majid Ebrahimi Warkiani, and Andrei V. Zvyagin. "Rapid and Label-Free Isolation of Tumour Cells from the Urine of Patients with Localised Prostate Cancer Using Inertial Microfluidics." Cancers 12, no. 1 (December 29, 2019): 81. http://dx.doi.org/10.3390/cancers12010081.

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During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco’s phosphate-buffered saline sample, where it demonstrated >85 (±6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa—Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.

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Xiong, Lei, Xiao Li, Dongsheng Chen, Si Li, and Liguo Luo. "GPC1-ALK: A novel ALK fusion in a patient with pulmonary sarcomatoid carcinoma." Lung Cancer 151 (January 2021): 104–5. http://dx.doi.org/10.1016/j.lungcan.2020.11.021.

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Cui, Shuang, Melissa Leyva–Vega, Ellen A. Tsai, Steven F. EauClaire, Joseph T. Glessner, Hakon Hakonarson, Marcella Devoto, Barbara A. Haber, Nancy B. Spinner, and Randolph P. Matthews. "Evidence From Human and Zebrafish That GPC1 Is a Biliary Atresia Susceptibility Gene." Gastroenterology 144, no. 5 (May 2013): 1107–15. http://dx.doi.org/10.1053/j.gastro.2013.01.022.

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King, Will Ray, and Jana Patton-Vogt. "Role of the Candida albicans glycerophosphocholine acyltransferase, Gpc1, in phosphatidylcholine biosynthesis and cell physiology." FASEB Journal 34, S1 (April 2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.05461.

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Palmer, Daniel A., Jill K. Thompson, Lie Li, Ashton Prat, and Ping Wang. "Gib2, A Novel Gβ-like/RACK1 Homolog, Functions as a Gβ Subunit in cAMP Signaling and Is Essential in Cryptococcus neoformans." Journal of Biological Chemistry 281, no. 43 (September 1, 2006): 32596–605. http://dx.doi.org/10.1074/jbc.m602768200.

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Canonical G proteins are heterotrimeric, consisting of α, β, and γ subunits. Despite multiple Gα subunits functioning in fungi, only a single Gβ subunit per species has been identified, suggesting that non-conventional G protein signaling exists in this diverse group of eukaryotic organisms. Using the Gα subunit Gpa1 that functions in cAMP signaling as bait in a two-hybrid screen, we have identified a novel Gβ-like/RACK1 protein homolog, Gib2, from the human pathogenic fungus Cryptococcus neoformans. Gib2 contains a seven WD-40 repeat motif and is predicted to form a seven-bladed β propeller structure characteristic of β transducins. Gib2 is also shown to interact, respectively, with two Gγ subunit homologs, Gpg1 and Gpg2, similar to the conventional Gβ subunit Gpb1. In contrast to Gpb1 whose overexpression promotes mating response, overproduction of Gib2 suppresses defects of gpa1 mutation in both melanization and capsule formation, the phenotypes regulated by cAMP signaling and associated with virulence. Furthermore, depletion of Gib2 by antisense suppression results in a severe growth defect, suggesting that Gib2 is essential. Finally, Gib2 is shown to also physically interact with a downstream target of Gpa1-cAMP signaling, Smg1, and the protein kinase C homolog Pkc1, indicating that Gib2 is also a multifunctional RACK1-like protein.

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Hasandoost, Leyla, Daniella Marx, Paul Zalzal, Oleg Safir, Mark Hurtig, Cina Mehrvar, Stephen D. Waldman, Marcello Papini, and Mark R. Towler. "Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model." Journal of Functional Biomaterials 12, no. 3 (August 5, 2021): 44. http://dx.doi.org/10.3390/jfb12030044.

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Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO2-CaO-SrO-P2O5-Ta2O5, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn2+ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone.

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Qiu, Wenli, Rong Chen, Xiao Chen, Huifeng Zhang, Lina Song, Wenjing Cui, Jingjing Zhang, Dandan Ye, Yifen Zhang, and Zhongqiu Wang. "Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreatic cancer." International Journal of Nanomedicine Volume 13 (October 2018): 6809–27. http://dx.doi.org/10.2147/ijn.s177993.

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Ke, Juntao, Shuaidan Zeng, Jianxiong Mao, Jianyao Wang, Jiao Lou, Jiaoyuan Li, Xueqin Chen, et al. "Common genetic variants of GPC1 gene reduce risk of biliary atresia in a Chinese population." Journal of Pediatric Surgery 51, no. 10 (October 2016): 1661–64. http://dx.doi.org/10.1016/j.jpedsurg.2016.05.009.

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Vermeesch, Joris R., Griet Mertens, Guido David, and Peter Marynen. "Assignment of the human glypican gene (GPC1) to 2q35–q37 by fluorescence in situ hybridization." Genomics 25, no. 1 (January 1995): 327–29. http://dx.doi.org/10.1016/0888-7543(95)80152-c.

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Li, Nan, Dan Li, Jiajia Pan, Raul Cachau, and Mitchell Ho. "Abstract 549: The IgG4 hinge with CD28 transmembrane domain mediates CAR dimerization and improves the activity of glypican 1-targeted CAR T cells in pancreatic cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 549. http://dx.doi.org/10.1158/1538-7445.am2022-549.

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Abstract Low antigen density has been suggested as a major cause of insufficient antitumor activity of chimeric antigen receptor (CAR) T cells. The impact of the hinge and the transmembrane (TM) domain on modulating CAR T cell reactivity is important to investigate. Here, we isolated a camel nanobody D4 recognizing glypican 1 (GPC1), a cell surface proteoglycan that is expressed in pancreatic cancer. We constructed a series of D4 4-1BBζ CARs differing only by their hinge (CD8 or IgG4) and TM (CD8 or CD28). D4 CARs containing a mutated IgG4 hinge and the CD28 TM, but not CD8 hinge with either TM, formed dimers in human T cells and resulted in improved stability of the CAR extracellular domain in a 3D structure model. The CAR dimerization increased phosphorylation of T cell signaling molecules, activated non-canonical NF-κB signaling after antigen stimulation. Consequently, the D4-IgG4 hinge-CD28TM CAR T cells triggered the most cytokine secretion and showed the best reactivity against low GPC1-expressing pancreatic tumor cells among all the D4 CARs in vitro and in vivo. Conversely, a CAR with mutations of the two cysteine residues in the IgG4 hinge disrupted CAR dimerization, damaged the formation of TM, and resulted in the loss of improved reactivity. Furthermore, adding extra spacers of CH3 or CH2CH3 between IgG4 hinge and CD28TM CAR attenuated the CAR activity. By optimizing the hinge and TM, our data indicated that 4-1BBζ CAR T cell activity can be optimized against low antigen density tumors. Citation Format: Nan Li, Dan Li, Jiajia Pan, Raul Cachau, Mitchell Ho. The IgG4 hinge with CD28 transmembrane domain mediates CAR dimerization and improves the activity of glypican 1-targeted CAR T cells in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 549.

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Karihaloo, Anil, Sujata Kale, Norman D. Rosenblum, and Lloyd G. Cantley. "Hepatocyte Growth Factor-Mediated Renal Epithelial Branching Morphogenesis Is Regulated by Glypican-4 Expression." Molecular and Cellular Biology 24, no. 19 (October 1, 2004): 8745–52. http://dx.doi.org/10.1128/mcb.24.19.8745-8752.2004.

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ABSTRACT The glypican (Gpc) family of cell surface heparan sulfate proteoglycans are expressed in a tissue-specific and developmentally regulated fashion. To determine if individual Gpcs can modulate heparin-binding growth factor signaling, we examined hepatocyte growth factor (HGF)-stimulated mitogenic, motogenic, and morphogenic responses of renal tubular cells expressing different Gpcs. Adult inner medullary collecting duct (IMCD) cells were found to express primarily Gpc4 and to proliferate, migrate, and form tubules with HGF, correlating with sustained extracellular signal-regulated kinase (ERK) activation. Embryonic IMCD cells expressing predominantly Gpc3 proliferated and migrated in response to HGF but activated ERK only transiently and failed to form tubules. Overexpressing Gpc-4 but not Gpc-3 or Gpc-1 led to sustained HGF-stimulated ERK activation and rescued the tubulogenic response in these cells. These results demonstrate that both signaling and phenotypic responses to HGF can be regulated by specific Gpc expression patterns.

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Li, Jian, Bo Li, Caiping Ren, Yuxiang Chen, Xiong Guo, Lin Zhou, Zha Peng, et al. "The clinical significance of circulating GPC1 positive exosomes and its regulative miRNAs in colon cancer patients." Oncotarget 8, no. 60 (August 24, 2017): 101189–202. http://dx.doi.org/10.18632/oncotarget.20516.

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Kong, Yuan-Mei, Ke Yuan, and Chun-Lin Wang. "Congenital biliary atresia caused by GPC1 gene mutation in Chinese siblings: A case report." World Journal of Clinical Cases 11, no. 3 (January 26, 2023): 629–34. http://dx.doi.org/10.12998/wjcc.v11.i3.629.

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Li, Fuchuan, Wen Shi, Mariana Capurro, and Jorge Filmus. "Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating Hedgehog signaling." Journal of Cell Biology 192, no. 4 (February 21, 2011): 691–704. http://dx.doi.org/10.1083/jcb.201008087.

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Glypican-5 (GPC5) is one of the six members of the glypican family. It has been previously reported that GPC5 stimulates the proliferation of rhabdomyosarcoma cells. In this study, we show that this stimulatory activity of GPC5 is a result of its ability to promote Hedgehog (Hh) signaling. We have previously shown that GPC3, another member of the glypican family, inhibits Hh signaling by competing with Patched 1 (Ptc1) for Hh binding. Furthermore, we showed that GPC3 binds to Hh through its core protein but not to Ptc1. In this paper, we demonstrate that GPC5 increases the binding of Sonic Hh to Ptc1. We also show that GPC5 binds to both Hh and Ptc1 through its glycosaminoglycan chains and that, unlike GPC3, GPC5 localizes to the primary cilia. Interestingly, we found that the heparan sulfate chains of GPC5 display a significantly higher degree of sulfation than those of GPC3. Based on these results, we propose that GPC5 stimulates Hh signaling by facilitating/stabilizing the interaction between Hh and Ptc1.

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Hong, Wei, Tingting Zhang, Junbin Yan, Jianshun Yu, Beihui He, Liyan Wu, Kannan Yao, Wei Mao, and Zhiyun Chen. "Bioinformatics analysis of an animal model of diet-induced nonalcoholic fatty liver disease with rapid progression." Experimental Biology and Medicine 247, no. 3 (November 13, 2021): 263–75. http://dx.doi.org/10.1177/15353702211055099.

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Nonalcoholic fatty liver disease (NAFLD) develops rapidly in high-fat diet (HFD) fed Mongolian gerbil ( Meriones unguiculatus). Here, we aim to explore the gene expression characteristics of Mongolian gerbil to better understand the underlying mechanism in this animal model. Mongolian gerbils were fed with normal diet or HFD for different periods. High-throughput sequencing was carried out on the hepatic mRNA and bioinformatics analysis was further performed. Eight hub genes Cd44, App, Cdc42, Cd68, Cxcr4, Csf1r, Adgre1, and Fermt3, which were involved in inflammation, fibrosis, and HCC were obtained. Four significant independent poor prognostic factors for HCC (GPC1, ARPC1B, DAB2, and CFL1) were screened out. qRT-PCR result showed that the above genes expressed high levels in different periods of modeling process. The findings of this study provide useful information for further studies on Mongolian gerbil NAFLD model.

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Behrangi, Ali, Alex Gardner, John T. Reager, Joshua B. Fisher, Daqing Yang, George J. Huffman, and Robert F. Adler. "Using GRACE to Estitmate Snowfall Accumulation and Assess Gauge Undercatch Corrections in High Latitudes." Journal of Climate 31, no. 21 (November 2018): 8689–704. http://dx.doi.org/10.1175/jcli-d-18-0163.1.

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Ten years of terrestrial water storage anomalies from the Gravity Recovery and Climate Experiment (GRACE) were used to estimate high-latitude snowfall accumulation using a mass balance approach. The estimates were used to assess two common gauge-undercatch correction factors (CFs): the Legates climatology (CF-L) utilized in the Global Precipitation Climatology Project (GPCP) and the Fuchs dynamic correction model (CF-F) used in the Global Precipitation Climatology Centre (GPCC) monitoring product. The two CFs can be different by more than 50%. CF-L tended to exceed CF-F over northern Asia and Eurasia, while the opposite was observed over North America. Estimates of snowfall from GPCP, GPCC-L (GPCC corrected by CF-L), and GPCC-F (GPCC corrected by CF-F) were 62%, 64%, and 46% more than GPCC over northern Asia and Eurasia. The GRACE-based estimate (49% more than GPCC) was the closest to GPCC-F. We found that as near-surface air temperature decreased, the products increasingly underestimated the GRACE-based snowfall accumulation. Overall, GRACE showed that CFs are effective in improving GPCC estimates. Furthermore, our case studies and overall statistics suggest that CF-F is likely more effective than CF-L in most of the high-latitude regions studied here. GPCP showed generally better skill than GPCC-L, which might be related to the use of satellite data or additional quality controls on gauge inputs to GPCP. This study suggests that GPCP can be improved if it employs CF-L instead of CF-F to correct for gauge undercatch. However, this implementation requires further studies, region-specific analysis, and operational considerations.

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Buscail, Etienne, Alexandre Chauvet, Pascaline Quincy, Olivier Degrandi, Camille Buscail, Isabelle Lamrissi, Isabelle Moranvillier, et al. "CD63-GPC1-Positive Exosomes Coupled with CA19-9 Offer Good Diagnostic Potential for Resectable Pancreatic Ductal Adenocarcinoma." Translational Oncology 12, no. 11 (November 2019): 1395–403. http://dx.doi.org/10.1016/j.tranon.2019.07.009.

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Zhang, Qin, Dennis K. Jeppesen, James N. Higginbotham, Ramona Graves-Deal, Vincent Q. Trinh, Marisol A. Ramirez, Yoojin Sohn, et al. "Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets." Nature Cell Biology 23, no. 12 (December 2021): 1240–54. http://dx.doi.org/10.1038/s41556-021-00805-8.

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AbstractExtracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer’s disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.

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Sergi, Consolato M., and Susan Gilmour. "Biliary Atresia: A Complex Hepatobiliary Disease with Variable Gene Involvement, Diagnostic Procedures, and Prognosis." Diagnostics 12, no. 2 (January 27, 2022): 330. http://dx.doi.org/10.3390/diagnostics12020330.

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The diagnosis of biliary atresia is still terrifying at the 3rd decade of the 21st century. In a department of neonatal intensive care unit, parents and physicians face a challenge with a jaundiced baby, who may or may not have a surgically correctable hepatopathy. The approach has been systematically evaluated, but the etiology remains ambiguous. The study of families with recurrent biliary atresia has been undertaken at a molecular level. The primary interest with this disease is to identify the etiology and change the treatment from symptomatic to curative. The occurrence of this obstructive cholangio-hepatopathy in well-known genetic syndromes has suggested just coincidental finding, but the reality can be more intriguing because some of these diseases may have some interaction with the development of the intrahepatic biliary system. Several genes have been investigated thoroughly, including ADD3 and GPC1 shifting the interest from viruses to genetics. In this review, the intriguing complexities of this hepatobiliary disease are highlighted.

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Li, Chunlong, Xuefei Du, Sheng Tai, Xiangyu Zhong, Zhidong Wang, Zhanliang Hu, Lei Zhang, et al. "GPC1 Regulated by miR-96-5p, Rather than miR-182-5p, in Inhibition of Pancreatic Carcinoma Cell Proliferation." International Journal of Molecular Sciences 15, no. 4 (April 14, 2014): 6314–27. http://dx.doi.org/10.3390/ijms15046314.

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Goshu, Habtamu Abera, Min Chu, Xiaoyun Wu, Bao Pengjia, Xue Zhi Ding, and Ping Yan. "Association study and expression analysis of GPC1 gene copy number variation in Chinese Datong yak (Bos grunniens) breed." Italian Journal of Animal Science 18, no. 1 (January 2, 2019): 820–32. http://dx.doi.org/10.1080/1828051x.2019.1586456.

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Journal articles on the topic 'GPC1'

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