[Growth pattern and metastatic behaviour of orthotopically metastatic model of human hepatocellular carcinoma in nude mice].

Growth pattern, metastatic behaviour and serial alph-a-fetoprotein (AFP) level of highly metastatic model of human hepatocellular carcinoma in nude mice (LCI-D20), which constructed by using orthotopic implantation of histologically intact patient specimens, were studied by implanting into the liver, subcutis and peritoneum of nude mice. Pathologic (by light and electronmicroscopic examination) and biologic (chromosome karyotype and DNA contents by flow cytometry) characteristics of LCI-D20 were also observed. The results showed that transplantability of LCI-D20 was 100% in 12 generations (passage time: 20 days) and all of these mice implanted tumors died within 40 days after transplantation due to serious metastasis. After LCI-D20 implanted into the liver of nude mice, growing implant-tumors in progress were negatively related to their double time during animal survival. LCI-D20 maintained 100% (70/70) metastatic rate in nude mice that showed early intrahepatic metastasis and late lymphatic and pulmonary metastasis. The high metastatic potentials of LCI-D20 tumor cells were kept in subcutis and peritoneum (70%, 100% respectively). The increase of the serial AFP secreting from the tumor cells was correlated with the implantation tumor growth rate (797.5 micrograms/L/5th week). The data from histological and electronmicroscopic findings, chromosome karyotype and DNA content analysis of the tumor cells revealed characteristics of human hepatocellular carcinoma. The results indicated that LCI-D20 exhibited the variety of clinical behaviours seen in hepatoma patients and it could be a useful model for investigating the metastasis mechanism of human hepatoma and anti-metastasis therapy.