{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:00:51Z","timestamp":1791216051155,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,11,21]],"date-time":"2002-11-21T00:00:00Z","timestamp":1037836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2003,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Glypican (GPC) family is a prototypical member of the cell\u2010surface 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\u2010GPC3 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\u2010derived cells. Overexpression of GPC3 modulated cell proliferation by inhibiting fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 7 (BMP\u20107) activity. An interaction of GPC3 and FGF2 was revealed by co\u2010immunoprecipitation, while GPC3 was found to inhibit BMP\u20107 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. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10856","type":"journal-article","created":{"date-parts":[[2002,12,12]],"date-time":"2002-12-12T14:09:22Z","timestamp":1039702162000},"page":"455-465","source":"Crossref","is-referenced-by-count":203,"title":["Glypican\u20103, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP\u20107 signaling"],"prefix":"10.1002","volume":"103","author":[{"given":"Yutaka","family":"Midorikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumpei","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Iwanari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Miyazono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiko","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Makuuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Aburatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,11,21]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113712"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106608200"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9831"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.0127"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80513-4"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199708)172:2<209::AID-JCP8>3.0.CO;2-S"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199803)174:3<310::AID-JCP5>3.0.CO;2-R"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.34.24113"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00723.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.1.F19"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-241"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.12.7574"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.6.1407"},{"key":"e_1_2_6_15_2","first-page":"807","article-title":"Frequent silencing of the GPC3 gene in ovarian cancer cell lines","volume":"59","author":"Lin H","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203322"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000920)89:5<418::AID-IJC4>3.0.CO;2-I"},{"key":"e_1_2_6_18_2","first-page":"58","article-title":"Expression of the novel mitoxantrone resistance associated gene MXR7 in colorectal malignancies","volume":"36","author":"Lage H","year":"1998","journal-title":"Int J Clin Pharmacol Ther"},{"key":"e_1_2_6_19_2","first-page":"5179","article-title":"Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution","volume":"57","author":"Hsu HC","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.4.558"},{"key":"e_1_2_6_21_2","first-page":"1504","article-title":"Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin","volume":"52","author":"Tsuda H","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4424"},{"key":"e_1_2_6_23_2","first-page":"889","article-title":"Differential gene expression profiles of scirrhus gastric cancer cells with high metastatic potential to peritoneum or lymph nodes","volume":"61","author":"Hippo Y","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/256495a0"},{"key":"e_1_2_6_25_2","first-page":"5562","article-title":"Glypican\u20101 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin\u2010binding growth factors in breast cancer cells","volume":"61","author":"Matsuda K","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.9.6075"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4105"},{"key":"e_1_2_6_28_2","first-page":"5562","article-title":"Glypican\u20101 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin\u2010binding growth factors in breast cancer cells","volume":"61","author":"Matsuda K","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.2054"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0182"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90512-W"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.133.2.405"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.34.24113"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)41979-X"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.1.255"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.10856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T17:11:54Z","timestamp":1697217114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.10856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11,21]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,2,10]]}},"alternative-id":["10.1002\/ijc.10856"],"URL":"https:\/\/doi.org\/10.1002\/ijc.10856","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11,21]]}}}