肝細胞癌の肝内浸潤および肝内転移様式 : 蛍光染色肝癌細胞を用いた正常肝および硬変肝における検討

Abstract

Despite intensive efforts in the treatment of hepatocellular carcinoma (HCC), its prognosis still remains poor mainly because of intrahepatic metastasis. In the majority of cases, HCC is found in conjunction with liver cirrhosis. It is, therefore, of great importance to investigate the invasive and metastatic behavior of HCC not only in the normal liver but also in the cirrhotic liver. To examine this, a liver cirrhosis model was produced by injecting thioacetamide intraperitoneally into mice. Murine HCC cells were labeled with the fluorescent carbocyanine dye, Dil, and implanted directly under the capsule of the cirrhotic and normal liver of syngeneic mice. Optimal conditions are described for labeling HCC cells with Dil. Dil-labeled HCC cells in the liver were observed under fluorescent and confocal microscopy. Histological analysis of the cirrhotic and normal liver revealed that implanted HCC cells migrated to and invaded the adjacent periportal regions, but not the adjacent centrolobular areas. This characteristic behavior of HCC was more evident in the cirrhotic liver compared to the normal liver. Furthermore, intrahepatic metastasis to unimplanted hepatic lobes was observed in the cirrhotic liver as early as 7 days after the implantation, while it was not detected in the normal liver even 4 weeks later. Thus, an orthotopic animal model for HCC with cirrhosis described here may be suitable for investigating the invasive and metastatic behavior of HCC. Furthermore, it is also indicat- ed that labeling tumor cells with a fluoresent dye followed by orthotopic implantation may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.