Human Monoclonal Antibody Targeting the Heparan Sulfate Chains of Glypican-3 Inhibits HGF-Mediated Migration and Motility of Hepatocellular Carcinoma Cells

PloS One
Wei GaoMitchell Ho

Abstract

Heparan sulfate proteoglycans (HSPGs) participate in many processes related to tumor development, including tumorigenesis and metastasis. HSPGs contain one or more heparan sulfate (HS) chains that are covalently linked to a core protein. Glypican-3 (GPC3) is a cell surface-associated HSPG that is highly expressed in hepatocellular carcinoma (HCC). GPC3 is involved in Wnt3a-dependent HCC cell proliferation. Our previous study reported that HS20, a human monoclonal antibody targeting the HS chains on GPC3, inhibited Wnt3a/β-catenin activation. In the current study, we showed that the HS chains of GPC3 could mediate HCC cells' migration and motility. Knocking down GPC3 or targeting the HS chains by HS20 inhibited HCC cell migration and motility. However, HS20 had no effect on GPC3 knockdown cells or GPC3 negative cells. In addition, an antibody that recognizes the core protein of GPC3 did not change the rate of cell motility. HCC cell migration and motility did not respond to either canonical or non-canonical Wnt induction, but did increase under hepatocyte growth factor (HGF) treatment. HS20-treated HCC cells exhibited less ability for HGF-mediated migration and motility. Furthermore, HS20 inhibited in vitro HCC spheroid formatio...Continue Reading

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Citations

Feb 5, 2016·Cancer Immunology, Immunotherapy : CII·Timothy T SpearMichael I Nishimura
Sep 27, 2016·Toxins·Bryan D Fleming, Mitchell Ho
Mar 21, 2017·Seminars in Cancer Biology·Leticia Oliveira-FerrerKarin Milde-Langosch
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Sep 13, 2019·Cancers·Takahiro Nishida, Hiroaki Kataoka
Aug 11, 2016·Oncotarget·Lilian Fedra CastilloMaría Giselle Peters
Jul 7, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Nan LiMitchell Ho
Apr 3, 2020·International Journal of Oncology·Yu-Xue GaoDe-Xi Chen
Jun 9, 2017·Molecular and Cellular Biochemistry·Vikrant RaiDevendra K Agrawal
Apr 10, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Na LiMitchell Ho
Mar 16, 2019·Frontiers in Oncology·Michael V OrtizLeonard H Wexler
Aug 21, 2019·Frontiers in Oncology·Aarti Kolluri, Mitchell Ho
Sep 11, 2018·Frontiers in Endocrinology·Arvindhan NagarajanNarendra Wajapeyee
Aug 14, 2018·Antibody Therapeutics·Mitchell Ho
Jul 25, 2019·Seminars in Cancer Biology·Nancy A Espinoza-Sánchez, Martin Götte
Oct 26, 2018·Trends in Cancer·Nan LiMitchell Ho

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Methods Mentioned

BETA
electrophoresis
Trans-well
transfection
pull down
xenograft
xenografts

Software Mentioned

GraphPad Prism

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