Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling
Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling
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DOI：
10.1002/ijc.10856
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发表时间：
2003-02-10
影响因子：
6.4
通讯作者：
Aburatani, H
中科院分区：
文献类型：
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作者：
Midorikawa, Y;Ishikawa, S;Aburatani, H
磷脂酰肌醇蛋白聚糖（GPC）家族是细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）的典型成员。HSPGs与生长因子相互作用，作为辅助受体，调节生长因子的活性。在这里，我们表明，基于寡核苷酸阵列分析，GPC 3在肝细胞癌（HCC）中上调。北方杂交结果显示，52例HCC中有29例（55.7%）GPC 3 mRNA表达上调。通过Western blot分析，发现GPC 3蛋白在6个肝癌细胞系HepG 2、Hep 3B、HT 17、HuH 6、HuH 7和PLC/PRF/5以及22个肿瘤中过表达（42.3%）。为了研究过表达的GPC 3在肝癌中的作用，我们分析了其对肝母细胞瘤衍生细胞的细胞生长的影响。GPC 3的过表达通过抑制成纤维细胞生长因子2（FGF 2）和骨形态发生蛋白7（BMP-7）的活性来调节细胞增殖。免疫共沉淀法证实GPC 3与FGF 2之间存在相互作用，而报告基因分析则证实GPC 3通过Smad途径抑制BMP-7信号转导。GPC 3对生长因子的调节可能有助于解释其在肝癌发生中的作用。此外，HCC细胞高水平表达GPC 3的能力可能作为HCC的新的肿瘤标志物。(C)2002 Wiley-Liss，Inc.
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. (C) 2002 Wiley-Liss, Inc.