Glypican 1

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Glypican-1''' (GPC1) is a protein that in humans is encoded by the ''GPC1'' gene.<ref name="Vermeesch_1995">{{cite journal | vauthors = Vermeesch JR, Mertens G, David G, Marynen P | title = Assignment of the human glypican gene (GPC1) to 2q35-q37 by fluorescence in situ hybridization | journal = Genomics | volume = 25 | issue = 1 | pages = 327–329 | date = January 1995 | pmid = 7774946 | doi = 10.1016/0888-7543(95)80152-C }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GPC1 glypican 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2817}}</ref> GPC1 is encoded by human ''GPC1'' gene located at 2q37.3.<ref name="Pan_2021">{{cite journal | vauthors = Pan J, Ho M | title = Role of glypican-1 in regulating multiple cellular signaling pathways | journal = American Journal of Physiology. Cell Physiology | volume = 321 | issue = 5 | pages = C846–C858 | date = November 2021 | pmid = 34550795 | pmc = 8616591 | doi = 10.1152/ajpcell.00290.2021 | doi-access = free }}</ref> GPC1 contains 558 amino acids with three predicted heparan sulfate chains.<ref name="Pan_2021" />

== Function ==

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with three heparan sulfate chains.<ref name="Pan_2021" /> 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.<ref name="entrez" />

== Interactions ==

Glypican 1 has been shown to interact with SLIT2.<ref name="pmid11375980">{{cite journal | vauthors = Ronca F, Andersen JS, Paech V, Margolis RU | title = Characterization of Slit protein interactions with glypican-1 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 31 | pages = 29141–29147 | date = August 2001 | pmid = 11375980 | doi = 10.1074/jbc.M100240200 | doi-access = free }}</ref>

== Clinical significance ==

This protein is involved in the misfolding of normal prion proteins in the cell membrane to the infectious prion form.<ref name = "Taylor_2009">{{cite journal | vauthors = Taylor DR, Whitehouse IJ, Hooper NM | title = Glypican-1 mediates both prion protein lipid raft association and disease isoform formation | journal = PLOS Pathogens | volume = 5 | issue = 11 | article-number = e1000666 | date = November 2009 | pmid = 19936054 | pmc = 2773931 | doi = 10.1371/journal.ppat.1000666 | doi-access = free }}</ref>

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.<ref name = "Melo_2015">{{cite journal | vauthors = Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D, Kalluri R | display-authors = 6 | title = Glypican-1 identifies cancer exosomes and detects early pancreatic cancer | journal = Nature | volume = 523 | issue = 7559 | pages = 177–182 | date = July 2015 | pmid = 26106858 | pmc = 4825698 | doi = 10.1038/nature14581 | bibcode = 2015Natur.523..177M }}{{Erratum|doi=10.1038/s41586-022-05062-9|pmid=36198804|https://retractionwatch.com/?s=sonia+melo ''Retraction Watch''}}</ref> However this conclusion is disputed.<ref>Discussions at www.pubpeer.com; https://pubpeer.com/publications/70714D8ACB8F13164A2752B4335F38#fb119888</ref> and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned.<ref name="pmid28376184">{{cite journal | vauthors = Balasenthil S, Huang Y, Liu S, Marsh T, Chen J, Stass SA, KuKuruga D, Brand R, Chen N, Frazier ML, Jack Lee J, Srivastava S, Sen S, McNeill Killary A | display-authors = 6 | title = A Plasma Biomarker Panel to Identify Surgically Resectable Early-Stage Pancreatic Cancer | journal = Journal of the National Cancer Institute | volume = 109 | issue = 8 | date = August 2017 | pmid = 28376184 | pmc = 6059209 | doi = 10.1093/jnci/djw341 }}</ref><ref name="pmid28335509">{{cite journal | vauthors = Chang JC, Kundranda M | title = Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma | journal = International Journal of Molecular Sciences | volume = 18 | issue = 3 | page = 667 | date = March 2017 | pmid = 28335509 | pmc = 5372679 | doi = 10.3390/ijms18030667 | doi-access = free }}</ref>

Therapeutic antibodies against GPC1 have been developed.<ref name="Pan_2022" /><ref name="pmid32228854" /><ref name=":0" /><ref name="Li_2023" /> GPC1 has been evaluated as a potential target for cancer therapy,<ref name="Pan_2021" /> including antibody-drug conjugates,<ref>{{cite journal | vauthors = Matsuzaki S, Serada S, Hiramatsu K, Nojima S, Matsuzaki S, Ueda Y, Ohkawara T, Mabuchi S, Fujimoto M, Morii E, Yoshino K, Kimura T, Naka T | display-authors = 6 | title = Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer | journal = International Journal of Cancer | volume = 142 | issue = 5 | pages = 1056–1066 | date = March 2018 | pmid = 29055044 | doi = 10.1002/ijc.31124 | doi-access = free }}</ref> CAR-T cell therapy,<ref name=":0">{{Cite journal| vauthors = Li N, Li D, Ren H, Torres M, Ho M |date=2019-07-01|title=Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer|journal=Immunology|volume=79 |issue=13_Supplement |page=2309 |publisher=American Association for Cancer Research|doi=10.1158/1538-7445.am2019-2309|s2cid=216597566 }}</ref><ref name="pmid32228854">{{cite journal | vauthors = Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, Takise Y, Tamiya M, Kamada H, Akiba H, Tsumoto K, Serada S, Naka T, Nishimura R, Nakagawa T, Kawakami Y | display-authors = 6 | title = GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab | journal = eLife | volume = 9 | issue = | date = March 2020 | pmid = 32228854 | pmc = 7108862 | doi = 10.7554/eLife.49392 | doi-access = free }}</ref><ref name="Li_2023" /> radiotherapy,<ref>{{cite journal | vauthors = Yeh MC, Tse BW, Fletcher NL, Houston ZH, Lund M, Volpert M, Stewart C, Sokolowski KA, Jeet V, Thurecht KJ, Campbell DH, Walsh BJ, Nelson CC, Russell PJ | display-authors = 6 | title = Targeted beta therapy of prostate cancer with ¹⁷⁷Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1) | journal = EJNMMI Research | volume = 10 | issue = 1 | page = 46 | date = May 2020 | pmid = 32382920 | pmc = 7206480 | doi = 10.1186/s13550-020-00637-x | doi-access = free }}</ref> bispecific T cell engager<ref>{{cite journal | vauthors = Lund ME, Howard CB, Thurecht KJ, Campbell DH, Mahler SM, Walsh BJ | title = A bispecific T cell engager targeting Glypican-1 redirects T cell cytolytic activity to kill prostate cancer cells | journal = BMC Cancer | volume = 20 | issue = 1 | page = 1214 | date = December 2020 | pmid = 33302918 | pmc = 7727117 | doi = 10.1186/s12885-020-07562-1 | doi-access = free }}</ref> and immunotoxins<ref name="Pan_2022">{{cite journal | vauthors = Pan J, Li N, Renn A, Zhu H, Chen L, Shen M, Hall MD, Qian M, Pastan I, Ho M | display-authors = 6 | title = GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling | journal = Molecular Cancer Therapeutics | volume = 21 | issue = 6 | pages = 960–973 | date = June 2022 | pmid = 35312769 | pmc = 9167738 | doi = 10.1158/1535-7163.MCT-21-0778 }}</ref> 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).<ref name="Li_2023">{{cite journal | vauthors = Li N, Quan A, Li D, Pan J, Ren H, Hoeltzel G, de Val N, Ashworth D, Ni W, Zhou J, Mackay S, Hewitt SM, Cachau R, Ho M | display-authors = 6 | title = The IgG4 hinge with CD28 transmembrane domain improves V_HH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer | journal = Nature Communications | volume = 14 | issue = 1 | page = 1986 | date = April 2023 | pmid = 37031249 | pmc = 10082787 | doi = 10.1038/s41467-023-37616-4 | bibcode = 2023NatCo..14.1986L }}</ref> The Ho lab also produced a dromedary camel V_HH nanobody called D4 specific for GPC1.<ref name="Li_2023" />The D4 V_HH nanobody-based CAR-T cells<ref name="Li_2023" /> and immunotoxins<ref name="Pan_2022" /> were active against pancreatic cancer in mice. Miltuximab, a chimeric antibody against GPC1, was tested in radioimmunotherapy models of prostate cancer.<ref>{{Cite journal |last1=Sabanathan |first1=Dhanusha |last2=Campbell |first2=Douglas |last3=Velonas |first3=Vicki |last4=Wissmueller |first4=Sandra |last5=Mazure |first5=Hubert |last6=Trifunovic |first6=Marko |last7=Poursoltan |first7=Pirooz |last8=Ho-Shon |first8=Kevin |last9=Mackay |first9=Tiffany |last10=Lund |first10=Maria |last11=Lu |first11=Yanling |last12=Roach |first12=Paul |last13=Bailey |first13=Dale |last14=Walsh |first14=Bradley |last15=Gillatt |first15=David |date=May 2021 |title=Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers |journal=Asia Oceania Journal of Nuclear Medicine and Biology |volume=9 |issue=2 |pages=86–100 |doi=10.22038/aojnmb.2021.55600.1386 |pmc=8255523 |pmid=34250138}}</ref>

== See also == * Glypican {{clear}} == References == {{reflist}}

== Further reading == {{refbegin |30em}} * {{cite journal | vauthors = Karthikeyan L, Maurel P, Rauch U, Margolis RK, Margolis RU | title = Cloning of a major heparan sulfate proteoglycan from brain and identification as the rat form of glypican | journal = Biochemical and Biophysical Research Communications | volume = 188 | issue = 1 | pages = 395–401 | date = October 1992 | pmid = 1417860 | doi = 10.1016/0006-291X(92)92398-H | doi-access = free }} * {{cite journal | vauthors = David G, Lories V, Decock B, Marynen P, Cassiman JJ, Van den Berghe H | title = Molecular cloning of a phosphatidylinositol-anchored membrane heparan sulfate proteoglycan from human lung fibroblasts | journal = The Journal of Cell Biology | volume = 111 | issue = 6 Pt 2 | pages = 3165–3176 | date = December 1990 | pmid = 2148568 | pmc = 2116352 | doi = 10.1083/jcb.111.6.3165 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Kleeff J, Ishiwata T, Kumbasar A, Friess H, Büchler MW, Lander AD, Korc M | title = The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer | journal = The Journal of Clinical Investigation | volume = 102 | issue = 9 | pages = 1662–1673 | date = November 1998 | pmid = 9802880 | pmc = 509114 | doi = 10.1172/JCI4105 }} * {{cite journal | vauthors = Gengrinovitch S, Berman B, David G, Witte L, Neufeld G, Ron D | title = Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular chaperone for VEGF165 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 16 | pages = 10816–10822 | date = April 1999 | pmid = 10196157 | doi = 10.1074/jbc.274.16.10816 | doi-access = free }} * {{cite journal | vauthors = Liang Y, Annan RS, Carr SA, Popp S, Mevissen M, Margolis RK, Margolis RU | title = Mammalian homologues of the Drosophila slit protein are ligands of the heparan sulfate proteoglycan glypican-1 in brain | journal = The Journal of Biological Chemistry | volume = 274 | issue = 25 | pages = 17885–17892 | date = June 1999 | pmid = 10364234 | doi = 10.1074/jbc.274.25.17885 | doi-access = free }} * {{cite journal | vauthors = Schofield KP, Gallagher JT, David G | title = Expression of proteoglycan core proteins in human bone marrow stroma | journal = The Biochemical Journal | volume = 343 Pt 3 | issue = Pt 3 | pages = 663–668 | date = November 1999 | pmid = 10527946 | pmc = 1220599 | doi = 10.1042/0264-6021:3430663 }} * {{cite journal | vauthors = Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B, Dhanabal M, Hanai JI, Venkataraman G, Shriver Z, Keiser N, Kalluri R, Zeng H, Mukhopadhyay D, Chen RL, Lander AD, Hagihara K, Yamaguchi Y, Sasisekharan R, Cantley L, Sukhatme VP | display-authors = 6 | title = Cell surface glypicans are low-affinity endostatin receptors | journal = Molecular Cell | volume = 7 | issue = 4 | pages = 811–822 | date = April 2001 | pmid = 11336704 | doi = 10.1016/S1097-2765(01)00225-8 | s2cid = 43358048 | doi-access = free }} * {{cite journal | vauthors = Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, Korc M | display-authors = 6 | title = Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells | journal = Cancer Research | volume = 61 | issue = 14 | pages = 5562–5569 | date = July 2001 | pmid = 11454708 }} * {{cite journal | vauthors = Alvarez K, Fadic R, Brandan E | title = Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy | journal = Journal of Cellular Biochemistry | volume = 85 | issue = 4 | pages = 703–713 | year = 2002 | pmid = 11968010 | doi = 10.1002/jcb.10184 | hdl-access = free | s2cid = 20243469 | hdl = 10533/173369 }} * {{cite journal | vauthors = Ding K, Mani K, Cheng F, Belting M, Fransson LA | title = Copper-dependent autocleavage of glypican-1 heparan sulfate by nitric oxide derived from intrinsic nitrosothiols | journal = The Journal of Biological Chemistry | volume = 277 | issue = 36 | pages = 33353–33360 | date = September 2002 | pmid = 12084716 | doi = 10.1074/jbc.M203383200 | doi-access = free }} * {{cite journal | vauthors = Belting M, Mani K, Jönsson M, Cheng F, Sandgren S, Jonsson S, Ding K, Delcros JG, Fransson LA | display-authors = 6 | title = Glypican-1 is a vehicle for polyamine uptake in mammalian cells: a pivital role for nitrosothiol-derived nitric oxide | journal = The Journal of Biological Chemistry | volume = 278 | issue = 47 | pages = 47181–47189 | date = November 2003 | pmid = 12972423 | doi = 10.1074/jbc.M308325200 | doi-access = free }} * {{cite journal | vauthors = Watanabe N, Araki W, Chui DH, Makifuchi T, Ihara Y, Tabira T | title = Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease | journal = FASEB Journal | volume = 18 | issue = 9 | pages = 1013–1015 | date = June 2004 | pmid = 15084524 | doi = 10.1096/fj.03-1040fje | doi-access = free | s2cid = 83560098 }} * {{cite journal | vauthors = Li J, Kleeff J, Kayed H, Felix K, Penzel R, Büchler MW, Korc M, Friess H | display-authors = 6 | title = Glypican-1 antisense transfection modulates TGF-beta-dependent signaling in Colo-357 pancreatic cancer cells | journal = Biochemical and Biophysical Research Communications | volume = 320 | issue = 4 | pages = 1148–1155 | date = August 2004 | pmid = 15249209 | doi = 10.1016/j.bbrc.2004.06.063 }} * {{cite journal | vauthors = Davies EJ, Blackhall FH, Shanks JH, David G, McGown AT, Swindell R, Slade RJ, Martin-Hirsch P, Gallagher JT, Jayson GC | display-authors = 6 | title = Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer | journal = Clinical Cancer Research | volume = 10 | issue = 15 | pages = 5178–5186 | date = August 2004 | pmid = 15297422 | doi = 10.1158/1078-0432.CCR-03-0103 | s2cid = 396257 | doi-access = }} {{refend}}