Glypican-1 (GPC1) is a protein that in humans is encoded by the GPC1gene.[5][6] GPC1 is encoded by human GPC1 gene located at 2q37.3.[7] GPC1 contains 558 amino acids with three predicted heparan sulfate chains.[7]
Function
Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with three heparan sulfate chains.[7] Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.[6]
This protein is involved in the misfolding of normal prion proteins in the cell membrane to the infectious prion form.[9]
In 2015 it was reported that the presence of this protein in exosomes in patients' blood is able to detect early pancreatic cancer with absolute specificity and sensitivity.[10] However this conclusion is disputed.[11] and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned.[12][13]
Therapeutic antibodies against GPC1 have been developed.[14][15][16][17] GPC1 has been evaluated as a potential target for cancer therapy,[7] including antibody-drug conjugates,[18] CAR-T cell therapy,[16][15][17] radiotherapy,[19] bispecific T cell engager[20] and immunotoxins[14] in preclinical studies. HM2 is a mouse monoclonal antibody targeting the C-terminal end of GPC1 developed by the laboratory of Mitchell Ho at the NCI, NIH (Bethesda, US).[17] The Ho lab also produced a dromedary camel VHH nanobody called D4 specific for GPC1.[17]The D4 VHH nanobody-based CAR-T cells[17] and immunotoxins[14] were active against pancreatic cancer in mice. Miltuximab, a chimeric antibody against GPC1, was tested in radioimmunotherapy models of prostate cancer.[21]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Vermeesch JR, Mertens G, David G, Marynen P (January 1995). "Assignment of the human glypican gene (GPC1) to 2q35-q37 by fluorescence in situ hybridization". Genomics. 25 (1): 327–329. doi:10.1016/0888-7543(95)80152-C. PMID7774946.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, et al. (July 2001). "Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells". Cancer Research. 61 (14): 5562–5569. PMID11454708.
Alvarez K, Fadic R, Brandan E (2002). "Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy". Journal of Cellular Biochemistry. 85 (4): 703–713. doi:10.1002/jcb.10184. hdl:10533/173369. PMID11968010. S2CID20243469.
