Chuma Makoto, Sakamoto Michiie, Yasuda Jun, Fujii Gen, Nakanishi Kazuaki, Tsuchiya Akira, Ohta Tsutomu, Asaka Masahiro, Hirohashi Setsuo
Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
J Hepatol. 2004 Oct;41(4):629-36. doi: 10.1016/j.jhep.2004.06.018.
BACKGROUND/AIMS: The molecular basis of the metastasis of hepatocellular carcinoma (HCC) is not fully understood. The aim of this study was to elucidate the crucial genes involved in metastasis of HCC.
We compared expression profiles among highly metastatic HCC cell lines and non-metastatic HCC cell lines by using oligonucleotide array to identify genes associated with metastasis. We further investigated the effect of identified gene on cell motility and metastasis in vitro and in vivo. Finally, we examined immunohistochemistry in human tissue samples.
We identified 39 genes whose expression levels were significantly correlated with metastatic ability (P<0.05). Of these genes, we further investigated cortactin, because this cortical actin-associated protein is a substrate of Src, whose activation has been shown to be involved in HCC cell migration and metastasis. Overexpression of cortactin in a non-metastatic HCC cell line increased cell motility, and resulted in metastasis in an orthotopic model. Furthermore, immunohistochemical expression of cortactin revealed its significant overexpression in HCC with intrahepatic metastasis compared with HCC without intrahepatic metastasis (P<0.005).
Overexpression of cortactin may play a role in the metastasis of HCC by influencing cell motility, and cortactin could be a sensitive marker for HCC with intrahepatic metastasis.
背景/目的：肝细胞癌（HCC）转移的分子基础尚未完全明确。本研究旨在阐明参与HCC转移的关键基因。
我们通过使用寡核苷酸阵列比较高转移性HCC细胞系和非转移性HCC细胞系之间的表达谱，以鉴定与转移相关的基因。我们进一步研究了所鉴定基因在体外和体内对细胞运动性和转移的影响。最后，我们检测了人体组织样本中的免疫组化情况。
我们鉴定出39个基因，其表达水平与转移能力显著相关（P<0.05）。在这些基因中，我们进一步研究了皮质肌动蛋白，因为这种与皮质肌动蛋白相关的蛋白质是Src的底物，其激活已被证明与HCC细胞迁移和转移有关。在非转移性HCC细胞系中过表达皮质肌动蛋白可增加细胞运动性，并在原位模型中导致转移。此外，与无肝内转移的HCC相比，皮质肌动蛋白的免疫组化表达显示其在有肝内转移的HCC中显著过表达（P<0.005）。
皮质肌动蛋白的过表达可能通过影响细胞运动性在HCC转移中起作用，并且皮质肌动蛋白可能是有肝内转移的HCC的一个敏感标志物。
