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Glypican‐3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP‐7 signaling
Author(s) -
Midorikawa Yutaka,
Ishikawa Shumpei,
Iwanari Hiroko,
Imamura Takeshi,
Sakamoto Hirohiko,
Miyazono Kohei,
Kodama Tatsuhiko,
Makuuchi Masatoshi,
Aburatani Hiroyuki
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10856
Subject(s) - glypican 3 , cancer research , smad , cell growth , biology , hepatoblastoma , downregulation and upregulation , cell culture , bone morphogenetic protein , fibroblast growth factor , carcinogenesis , growth factor , microbiology and biotechnology , western blot , cell , signal transduction , hepatocellular carcinoma , chemistry , cancer , medicine , biochemistry , gene , receptor , genetics
The Glypican (GPC) family is a prototypical member of the cell‐surface heparan sulfate proteoglycans (HSPGs). The HSPGs have been demonstrated to interact with growth factors, act as coreceptors and modulate growth factor activity. Here we show that based on oligonucleotide array analysis, GPC3 was upregulated in hepatocellular carcinoma (HCC). By northern blot analysis, GPC3 mRNA was found to be upregulated in 29 of 52 cases of HCC (55.7%). By Western blot analysis carried out with a monoclonal anti‐GPC3 antibody we generated, the GPC3 protein was found to be overexpressed in 6 hepatoma cell lines, HepG2, Hep3B, HT17, HuH6, HuH7 and PLC/PRF/5, as well as 22 tumors (42.3%). To investigate the role of overexpressed GPC3 in liver cancer, we analyzed its effects on cell growth of hepatoblastoma‐derived cells. Overexpression of GPC3 modulated cell proliferation by inhibiting fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 7 (BMP‐7) activity. An interaction of GPC3 and FGF2 was revealed by co‐immunoprecipitation, while GPC3 was found to inhibit BMP‐7 signaling through the Smad pathway by reporter gene assay. The modulation of growth factors by GPC3 may help explain its role in liver carcinogenesis. In addition, the ability of HCC cells to express GPC3 at high levels may serve as a new tumor marker for HCC. © 2002 Wiley‐Liss, Inc.