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]

GPC1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGPC1, glypican, Glypican 1
External IDsOMIM: 600395; MGI: 1194891; HomoloGene: 20477; GeneCards: GPC1; OMA:GPC1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002081

NM_016696

RefSeq (protein)

NP_002072

NP_057905

Location (UCSC)Chr 2: 240.44 – 240.47 MbChr 1: 92.76 – 92.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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

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Glypican 1 has been shown to interact with SLIT2.[8]

Clinical significance

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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]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000063660Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034220Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b "Entrez Gene: GPC1 glypican 1".
  7. ^ a b c d 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ Discussions at www.pubpeer.com; https://pubpeer.com/publications/70714D8ACB8F13164A2752B4335F38#fb119888
  12. ^ 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.
  13. ^ 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.
  14. ^ a b c 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.
  15. ^ a b 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.
  16. ^ a b 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.
  17. ^ a b c d e 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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

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