| Hepatocellular carcinoma (HCC) is the 2nd most common cause of death from cancer in China, which accounts for 18.8 percent of the number of total death patients with malignant tumors. A large of populations with hepatitis virus B or cirrhosis attribute to the higher incidence.Surgical rescection remains an important approach for a curable outcome of hepatocellular carcinoma, however recurrence and metastasis are quite common after curative rescection, which are main obstacles to successful treatment. So it was emphasized to understand the molecular mechanisms of process of metastasis and interactions between the metastatic tumor cells and host environment. A new class of cancer therapies that targets the pathological communication interface is currently under development.The process of tumor metastasis is non random and highly selective and consists of a series of sequential, interrelated steps. Primary neoplasms are biologically heterogenous. To produce clinically relevant lesions, metastatic cells must complete all steps of this process, depending on multiple and complex interactions of metastatic cells with host homeostatic mechanisms. Metastases develop only when the "seed"(certain tumor cells with metastatic ability) and the "soil"(organs providing growth advantage to the seeds) are compatible. Lung is the most common site in addition to intrahepatic spread in HCC, which accounts for the 90 percent of blood vessel metastasis. Two clones with high (MHCC97-H) and low(MHCC97-L) metastatic potentials were developed in our institute, which the pulmonary metastatic rate was 100% vs 40%.To understand the mechanism of organ-specifc metastasis in HCC, extracts from different tissues were performed to induce responsive ability to MHCC97-H and MHCC97-L aiming at proving the hypothsis of "seed" and "soil". Moreover, the relavant molecular was purified by using strategies for protein purification for development of new cancer therapy.Part OneEffect of Lung Extracts on Migration and Invasion in Human Hepatocellular Carcinoma Cells with High and Low Metastatic PotentialsBased on the evidence that lung is the most common site to which liver tumor cells preferentially metastasizes, we studied the promoting ability of extracts of lung, liver, spleen, kidney on the migration and invasion in human hepatocellular carcinoma cells with different metastatic potentials. Firstly, extracts of liver, lung, spleen, and kidney from C57BL/6 female mice were prepared for the chemoinvasion assay. The in vitro invasion assay was used to compare the ability of migration and invasion of human hepatocellular carcinoma cells, MHCC97-H and MHCC97-L, with different metastatic potentials induced by extracts of lung, liver, spleen, kidney. The results showed the number of cells in response to extracts of lung, liver, spleen, kidney and serum-free DMEM in MHCC97-H were 64±10, 6±2, 3±1, 22±4, 1±0, respectively. In comparison to the extracts of liver, spleen and kidney, lung extracts showed significant differences to promote the migratory and invasive ability for MHCC97-H(P<0.001). The number of cells in response to extracts of lung, liver, spleen, kidney and serum-free DMEM in MHCC97-L were 20±6, 2±0,1±1, 6±2, 0±0, respectively. The responsive ability induced by lung extracts was higher in MHCC97-H than in MHCC97-L.These results supported the hypothesis of "seed" and "soil" and the metastatic pattern in our model. Organ-specific metastasis of primary liver cancer may be mediated by host environment. The effect of lung extracts on migration and invasion in HCC indicated there are some soluble factors to play an important role. Part TwoStudy on the Mechanism of Migration and Invasion in Human Hepatocellular Carcinoma Mediated by Lung Extracts from Mice It is necessary condition for degradation of the matrigel and migratory ability to penitrate the filter in vitro chemoinvasion assay. Secretion of proteolytic enzyme andinvadopodia formation is associated with the invasive behavior of tumors. To st...
|
PDF Full Text Request