Gotoh Masahiro, Sakamoto Michiie, Kanetaka Kengo, Chuuma Makoto, Hirohashi Setsuo
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Pathol Int. 2002 Jan;52(1):19-24. doi: 10.1046/j.1440-1827.2002.01316.x.
Human hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies. In order to identify genes involved in HCC progression, we conducted a differential display analysis and found osteopontin (OPN) to be overexpressed in HCC. OPN is known to be a secreted adhesive glycoprotein, associated with tumorigenesis and metastasis in several cancers. Quantitative polymerase chain reaction analysis of 30 HCC cases revealed the average ratio of OPN to glyceraldehyde-3-phosphate dehydrogenase in tumors to be significantly higher than that in the surrounding non-cancerous liver (4.7 +/- 1.6 vs 0.18 +/- 0.04, P = 0.0072). Immunohistochemistry confirmed the OPN protein was expressed mainly on cancer cells, and was positive in 12 of 30 HCC, most of which showed transcript overexpression. Both OPN transcript and OPN protein were significantly overexpressed in HCC with capsular infiltration, compared with HCC without capsular infiltration. Moreover, OPN-positive cancer cells were often dispersed in the periphery of cancer nodules and were adjacent to stromal cells. Although OPN overexpression was not related to vascular invasion or intrahepatic metastasis, OPN was suggested to play a role in HCC, especially in cancer-stromal interactions.
人类肝细胞癌（HCC）是最常见且侵袭性最强的恶性肿瘤之一。为了鉴定参与HCC进展的基因，我们进行了差异显示分析，发现骨桥蛋白（OPN）在HCC中过表达。已知OPN是一种分泌型黏附糖蛋白，与多种癌症的肿瘤发生和转移相关。对30例HCC病例进行定量聚合酶链反应分析发现，肿瘤中OPN与甘油醛-3-磷酸脱氢酶的平均比值显著高于周围非癌性肝组织（4.7±1.6对0.18±0.04，P = 0.0072）。免疫组织化学证实OPN蛋白主要在癌细胞上表达，30例HCC中有12例呈阳性，其中大多数显示转录本过表达。与无包膜浸润的HCC相比，有包膜浸润的HCC中OPN转录本和OPN蛋白均显著过表达。此外，OPN阳性癌细胞常分散在癌结节周边并与基质细胞相邻。虽然OPN过表达与血管侵犯或肝内转移无关，但提示OPN在HCC中起作用，尤其是在癌-基质相互作用中。
