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]
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]
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]