E–Cadherin Is Involved in the Intrahepatic Metastasis of Hepatocellular Carcinoma

Abstract

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.