Osada T, Sakamoto M, Ino Y, Iwamatsu A, Matsuno Y, Muto T, Hirohashi S
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Hepatology. 1996 Dec;24(6):1460-7. doi: 10.1053/jhep.1996.v24.pm0008938181.
In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM produced multiple liver metastasis, whereas subline Li7NM never did so after intrasplenic injection into nude mice. Two-dimensional gel electrophoresis and immunoblot analysis showed that only Li7NM expressed vimentin and lacked E-cadherin expression, indicating that this clone had undergone epithelial-mesenchymal transition. We then transfected mouse E-cadherin complementary DNA into Li7NM cells and found that the transfectant cells (EM16.21B.3) formed liver metastasis (8/16 mice) after intrasplenic injection and liver tumors (11/13 mice) after intrahepatic injection, whereas the control cell line formed no tumors. These results suggest that E-cadherin plays an important role in the process of intrahepatic metastasis of HCC.
在人类肝细胞癌（HCC）中，肝脏是转移的主要靶器官，这被称为肝内转移。为了分析这种转移的机制，我们从人类HCC细胞系Li7建立了两个亚系。亚系Li7HM产生了多个肝转移灶，而亚系Li7NM在脾内注射到裸鼠后从未发生过这种情况。二维凝胶电泳和免疫印迹分析表明，只有Li7NM表达波形蛋白且缺乏E-钙黏蛋白表达，表明该克隆经历了上皮-间质转化。然后我们将小鼠E-钙黏蛋白互补DNA转染到Li7NM细胞中，发现转染后的细胞（EM16.21B.3）在脾内注射后形成了肝转移灶（16只小鼠中有8只），在肝内注射后形成了肝肿瘤（13只小鼠中有11只），而对照细胞系未形成肿瘤。这些结果表明，E-钙黏蛋白在HCC肝内转移过程中起重要作用。
