Glypican 1

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An Error has occurred retrieving Wikidata item for infobox Glypican-1 (GPC1) is a protein that in humans is encoded by the GPC1 gene.[1][2] GPC1 is encoded by human GPC1 gene located at 2q37.3.[3] GPC1 contains 558 amino acids with three predicted heparan sulfate chains.[3]

Function

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with three heparan sulfate chains.[3] 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.[2]

Interactions

Glypican 1 has been shown to interact with SLIT2.[4]

Clinical significance

This protein is involved in the misfolding of normal prion proteins in the cell membrane to the infectious prion form.[5] 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.[6] However this conclusion is disputed.[7] and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned.[8][9] Therapeutic antibodies against GPC1 have been developed.[10][11][12][13] GPC1 has been evaluated as a potential target for cancer therapy,[3] including antibody-drug conjugates,[14] CAR-T cell therapy,[12][11][13] radiotherapy,[15] bispecific T cell engager[16] and immunotoxins[10] 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).[13] The Ho lab also produced a dromedary camel VHH nanobody called D4 specific for GPC1.[13]The D4 VHH nanobody-based CAR-T cells[13] and immunotoxins[10] were active against pancreatic cancer in mice. Miltuximab, a chimeric antibody against GPC1, was tested in radioimmunotherapy models of prostate cancer.[17]

See also

References

  1. 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. PMID 7774946.
  2. 2.0 2.1 "Entrez Gene: GPC1 glypican 1".
  3. 3.0 3.1 3.2 3.3 Pan J, Ho M (November 2021). "Role of glypican-1 in regulating multiple cellular signaling pathways". American Journal of Physiology. Cell Physiology. 321 (5): C846–C858. doi:10.1152/ajpcell.00290.2021. PMC 8616591. PMID 34550795.
  4. Ronca F, Andersen JS, Paech V, Margolis RU (August 2001). "Characterization of Slit protein interactions with glypican-1". The Journal of Biological Chemistry. 276 (31): 29141–29147. doi:10.1074/jbc.M100240200. PMID 11375980.
  5. Taylor DR, Whitehouse IJ, Hooper NM (November 2009). "Glypican-1 mediates both prion protein lipid raft association and disease isoform formation". PLOS Pathogens. 5 (11): e1000666. doi:10.1371/journal.ppat.1000666. PMC 2773931. PMID 19936054.
  6. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. (July 2015). "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer". Nature. 523 (7559): 177–182. Bibcode:2015Natur.523..177M. doi:10.1038/nature14581. PMC 4825698. PMID 26106858.
  7. Discussions at www.pubpeer.com; https://pubpeer.com/publications/70714D8ACB8F13164A2752B4335F38#fb119888
  8. Balasenthil S, Huang Y, Liu S, Marsh T, Chen J, Stass SA, et al. (August 2017). "A Plasma Biomarker Panel to Identify Surgically Resectable Early-Stage Pancreatic Cancer". Journal of the National Cancer Institute. 109 (8). doi:10.1093/jnci/djw341. PMC 6059209. PMID 28376184.
  9. Chang JC, Kundranda M (March 2017). "Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma". International Journal of Molecular Sciences. 18 (3): 667. doi:10.3390/ijms18030667. PMC 5372679. PMID 28335509.
  10. 10.0 10.1 10.2 Pan J, Li N, Renn A, Zhu H, Chen L, Shen M, et al. (June 2022). "GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling". Molecular Cancer Therapeutics. 21 (6): 960–973. doi:10.1158/1535-7163.MCT-21-0778. PMC 9167738. PMID 35312769.
  11. 11.0 11.1 Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, et al. (March 2020). "GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab". eLife. 9. doi:10.7554/eLife.49392. PMC 7108862. PMID 32228854.
  12. 12.0 12.1 Li N, Li D, Ren H, Torres M, Ho M (2019-07-01). "Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer". Immunology. 79 (13_Supplement). American Association for Cancer Research: 2309. doi:10.1158/1538-7445.am2019-2309. S2CID 216597566.
  13. 13.0 13.1 13.2 13.3 13.4 Li N, Quan A, Li D, Pan J, Ren H, Hoeltzel G, et al. (April 2023). "The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer". Nature Communications. 14 (1): 1986. Bibcode:2023NatCo..14.1986L. doi:10.1038/s41467-023-37616-4. PMC 10082787. PMID 37031249.
  14. Matsuzaki S, Serada S, Hiramatsu K, Nojima S, Matsuzaki S, Ueda Y, et al. (March 2018). "Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer". International Journal of Cancer. 142 (5): 1056–1066. doi:10.1002/ijc.31124. PMID 29055044.
  15. Yeh MC, Tse BW, Fletcher NL, Houston ZH, Lund M, Volpert M, et al. (May 2020). "Targeted beta therapy of prostate cancer with 177Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1)". EJNMMI Research. 10 (1): 46. doi:10.1186/s13550-020-00637-x. PMC 7206480. PMID 32382920.
  16. Lund ME, Howard CB, Thurecht KJ, Campbell DH, Mahler SM, Walsh BJ (December 2020). "A bispecific T cell engager targeting Glypican-1 redirects T cell cytolytic activity to kill prostate cancer cells". BMC Cancer. 20 (1): 1214. doi:10.1186/s12885-020-07562-1. PMC 7727117. PMID 33302918.
  17. Sabanathan, Dhanusha; Campbell, Douglas; Velonas, Vicki; Wissmueller, Sandra; Mazure, Hubert; Trifunovic, Marko; Poursoltan, Pirooz; Ho-Shon, Kevin; Mackay, Tiffany; Lund, Maria; Lu, Yanling; Roach, Paul; Bailey, Dale; Walsh, Bradley; Gillatt, David (May 2021). "Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers". Asia Oceania Journal of Nuclear Medicine and Biology. 9 (2): 86–100. doi:10.22038/aojnmb.2021.55600.1386. PMC 8255523. PMID 34250138.

Further reading