Glypican 1
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
Glypican-1 (GPC1) is a protein that in humans is encoded by the GPC1 gene.[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]
Interactions
Clinical significance
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]