Optimization Of A Metastatic Cell Model Of Human Hepatocellular Carcinoma And Study On The Mechanisms Of Metastasis

Surgical resection remains an important approach for a curable outcome of hepatocellular carcinoma (HCC). However, metastasis and recurrence are quite common, being as high as 40% to 50% five years after curative resection even for small liver cancers less than 5 cm in diameter. Invasion and metastasis have become the most prominent obstacles to further improvement of clinical treatment efficacy. A good study model and appropriate methodology are essential for the thorough understanding of the biological behaviors of liver cancer cells. In this regard, nude mice model of human hepatocellular carcinoma (LTNM1,LTNM2,LTNM3,LTNM4 ), nude rat model of human hepatocellular carcinoma (LTNR1,LTNR2), nude mice model of highly metastatic human hepatocellular carcinoma (LCI-D20), and highly metastatic human hepatocellular carcinoma cell line MHCC97 have been established and extensively studied. Although most tumors originate from a single mutant cell that is genetically unstable, the tumor cells undergo constant changes in their evolution process due to their unstable natural and the selective pressure of their living surroundings, thus producing a great variety of cells with different degrees of differentiation and phenotype. Therefore a solid tumor mass is composed of tumor cell clones of different biological behavior, a phenomenon known as tumor heterogeneity. As one of the most fundamental properties of cancer, tumor heterogeneity exists in every aspect of its biological behavior, including metastasis. This metastatic heterogeneity means that not all tumor cells from a heterogeneous primary tumor mass have the invasive and metastatic capability. Only some subpopulations possess the metastatic potential and ultimately produce metastases. Moreover, not all the cells in these metastatic subpopulations have the same metastatic potential. In this context, MHCC97 cell line is also a heterogeneous population, containing tumor cell subpopulations of different biological characteristics, including metastatic potential. The main purpose of the current study was to optimize the metastatic human hepatocellular cell line MHCC97, separate and select cells of different metastatic behavior, in order to establish a cell model system...