Establishment and characterization of liver metastatic model of human hepatoma in nude mice

We succeeded in producing the liver metastatic model of human hepatocellular carcinoma in athymic nude mice.The tumor, which was surgically obtained from a 59-year-old man with macro-trabecular hepatoma, was cut into small pieces and inoculated subcutaneously in athymic BALB/c nude mice. This transplanted tumor showed spontaneous liver metastases in 100% after the 3rd generation. There were also a few metastases in the spleen and lung. The metastatic liver tumors were resected and transplanted subcutaneously in other nude mice and, at present, the 18th generation has been maintained with 100% metastasizing characterization. All mice inoculated with this tumor were dead within 8 weeks due to liver metastases. The expression of intercellular adhesion molecule-1 (ICAM-1) was recognized on this tumor surface, however, a metastasizing capacity of this tumor could not be inhibited by pre-treatment of tumors with antibody against ICAM-1. Human leukocyte antigen (HLA) class I was also recognized, but lymphocyte function-associated antigen-1 (LFA-1) was not recognized. In the serum of tumor-transplanted nude mice or the medium of in vitro tumore culture, IL-1, IL-6 and type IV collagenase were not shown. This tumor also did not show the human platelet-aggregating activity. This spontaneous liver metastatic model was very rare and it was suggested that this model could be a useful tool for investigating the mechanism of liver metastasis of human hepatoma.