First Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Anticancer Res. 2010 Dec;30(12):5055-61.
To investigate the expression and significance of glypican-3 (GPC3) in human hepatocellular carcinoma (HCC).
DNA chips were used to measure the expression of mRNAs for members of the glypican and syndecan families of heparan sulfate proteoglycans (HSPGs) in normal liver tissue, non-tumor tissues and HCC. GPC3 protein expression was investigated by immunohistochemical staining in the tissues samples and Western blotting in human HCC cell lines. In addition, the levels of GPC3 protein in the blood were determined by ELISA.
Only the expression of GPC3 was found to be markedly elevated in HCCs. In the human HCC cell lines, GPC3 expression was consistently observed, and was mainly located in the cell membrane and cytoplasm. Immunohistochemistry showed a tendency for overall staining of the cytoplasm of cells in the liver carcinoma tissues, but the cell membrane was preferentially stained in poorly differentiated HCC when compared with well-differentiated HCC. Moreover, the cell membrane was preferentially stained in metastatic lesions of HCC when compared with primary HCC lesions. Non-tumor tissues and cholangiocellular carcinoma tissues were not stained. In addition, using HepG2 cells, AG490 and piceatannol, which are signal transducer and activator of transcription 3 (STAT3) inhibitors, each increased the amount of GPC3 mRNA expressed. Assay of the circulating levels of GPC3 protein in chronic liver disease and HCC found that serum GPC3 protein levels were significantly elevated in the latter.
GPC3 is highly expressed in HCC, and its expression pattern differs according to the degree of cell differentiation. In addition, the expression of GPC3 is regulated by Janus kinase-STAT signaling. GPC3 shows potential as a tumor biomarker for HCC that can be used for molecularly targeted therapy.
研究磷脂酰聚糖-3（GPC3）在人肝细胞癌（HCC）中的表达及意义。
采用 DNA 芯片检测正常肝组织、非肿瘤组织和 HCC 组织中糖胺聚糖蛋白聚糖家族和 syndecan 家族成员的 mRNA 表达。用免疫组织化学染色和 Western blot 检测组织样本中 GPC3 蛋白的表达，并检测人 HCC 细胞系中 GPC3 蛋白的表达。此外，通过 ELISA 法测定血液中 GPC3 蛋白的水平。
仅发现 GPC3 在 HCC 中表达明显上调。在人 HCC 细胞系中，始终观察到 GPC3 表达，主要位于细胞膜和细胞质中。免疫组化显示肝癌组织细胞的细胞质整体染色倾向，但与高分化 HCC 相比，低分化 HCC 更倾向于细胞膜染色。此外，与原发性 HCC 病变相比，转移性 HCC 病变更倾向于细胞膜染色。非肿瘤组织和胆管细胞癌组织均未染色。此外，使用 HepG2 细胞和信号转导和转录激活因子 3（STAT3）抑制剂 AG490 和白藜芦醇，发现每种抑制剂均增加了表达的 GPC3 mRNA 量。检测慢性肝病和 HCC 患者循环中 GPC3 蛋白的水平发现，后者血清 GPC3 蛋白水平显著升高。
GPC3 在 HCC 中高度表达，其表达模式根据细胞分化程度而异。此外，GPC3 的表达受 Janus 激酶-STAT 信号通路调节。GPC3 有望成为 HCC 的肿瘤标志物，可用于分子靶向治疗。
