Glypican 1

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

Glypican 1 has been shown to interact with SLIT2.{{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 }}

This protein is involved in the misfolding of normal prion proteins in the cell membrane to the infectious prion form.{{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 | pages = e1000666 | date = November 2009 | pmid = 19936054 | pmc = 2773931 | doi = 10.1371/journal.ppat.1000666 | doi-access = free }}

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.{{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 }} However this conclusion is disputed.Discussions at www.pubpeer.com; https://pubpeer.com/publications/70714D8ACB8F13164A2752B4335F38#fb119888 and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned.{{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 }}{{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 }}

Therapeutic antibodies against GPC1 have been developed. GPC1 has been evaluated as a potential target for cancer therapy, including antibody-drug conjugates,{{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 }} CAR-T cell therapy,{{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|url=http://dx.doi.org/10.1158/1538-7445.am2019-2309|journal=Immunology|volume=79 |issue=13_Supplement |page=2309 |publisher=American Association for Cancer Research|doi=10.1158/1538-7445.am2019-2309|s2cid=216597566 }}{{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 }} radiotherapy,{{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 | pages = 46 | date = May 2020 | pmid = 32382920 | pmc = 7206480 | doi = 10.1186/s13550-020-00637-x | doi-access = free }} bispecific T cell engager{{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 | pages = 1214 | date = December 2020 | pmid = 33302918 | pmc = 7727117 | doi = 10.1186/s12885-020-07562-1 | doi-access = free }} and immunotoxins{{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 }} 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).{{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 | pages = 1986 | date = April 2023 | pmid = 37031249 | pmc = 10082787 | doi = 10.1038/s41467-023-37616-4 | bibcode = 2023NatCo..14.1986L }} The Ho lab also produced a dromedary camel V_HH nanobody called D4 specific for GPC1.The D4 V_HH nanobody-based CAR-T cells and immunotoxins were active against pancreatic cancer in mice. Miltuximab, a chimeric antibody against GPC1, was tested in radioimmunotherapy models of prostate cancer.{{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 |url=https://doi.org/10.22038/aojnmb.2021.55600.1386 |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}}

• Glypican

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• {{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 }}
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• {{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 }}
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