Role Of Cell Adhesion Molecules And Gap Junctional Intercellular Communication In The Invasion And Metastasis Of Lung Cancer And Study Of Drugs Regulation

Most patients with cancer have appeared metastasis when they are diagnosed. It is a very complex and important problem in treatment of cancer, Although the primary tumor can be resected or treated with irradiation and immunotherapy, the efficiency rate is very low. Clinical results demonstrated that most of patients with cancer die of metastasis. The primary lung cancer is a kind of common tumor, which mortality has been at peak in those of malignant tumors for the time being. The majority of cases with lung cancer have been disseminated when the diagnosis is ratified. For the other minorities, the primary locations are still limited, so the surgery is indispensable. The reattack incident, not survival rate, could be improved by adjuvant postoperative chemotherapy. Surgery alone only adapts to non-small lung cancers in their stage I or stage II, even that, 50% of the patients in stage I is fatally stricken by recurrent attack. The best choice of treatment for the lung cancer is surgery, but the major death causation is metastasis after operation. Whether to treat lung cancer patients and prevent the cancer from recurrence or metastasis after operation successfully is critical.The cell adhesion molecules(CAM) are biological mediators responsi -ble for cell-cell and cell-matrix interactions, including cadherins, integrins, an immunoglobulin superfamily selectins, CD44 and other CAM. Recent evidence indicates that changes in the expression and function of these molecules are thought to play an essential role in the process of tumor invasion and metastasis and might be used in the future as prognostic factors. Adhesive interactions between metastatic tumor cells and theblood vessel endothelium are believed to be important in a blood borne metastatic process. Inhibition of these interaction would be of potential importance to obtain a clue for the mechanism of metastasis and to develop the method for its prevention.Gap junctional intercellular communication (GJIC) is important for cell growth, tissue differentiation and homeostasis. GJIC has been linked previously to tumorigenesis and progression toward metastasis. In tumori-genesis, a breakdown in homospecific and heterospecific coupling has been demonstrated to precede neoplasia and has been hypothesized as necessary to maintain malignant phenotype transformation. Some experimental im plying that tumor cell/endothelial cell communication is mediated by gap junctional channels. The direct cytoplasmic transfer of tumor metabolites to the endothelium may affect tumor cell extravasation by inducing localiz -ed endothelial cell retraction and exposure of subendothelial matrix to adherent tumor cells.To explore this possibility, we examined the hypothesis that metastatic potential correlates with gap junction function and CAM expression quantified in vitro and vivo.Studies of Regulative Drug and Correlative Mechanism on Growthand Metastasis of Human Lung Tumor PG Cell Lines1. Methods To explore the effects of intracellular calcium concentration, CD44 protein expression, gap junction intercellular communication (GJIC) and Cx43 on growth and metastasis of PG cell lines. The antiproliferation effects of three different concentration of tea polyphenols on PG cell lines were determined with MTT assay. Laser scanning confocal mircroscopy and flow cytometry techniques were used to determine the changes of intracellular calcium concentration, CD44 protein expression cell cycle distribution and GJIC after treatment with tea polyphenols.2. Results Three different concentrations dose-dependently inhibited the proliferation of PG cell lines. It caused a decline in the proportion of cells in S and G2/M phase, blacked the cell cycle progression in GO/Gl phase and reduced the proliferation index of PG cell lines. Compared with control group, intracellular calcium concentration, GJIC and Cx43 are gradually increased, the expression of CD44 protein are gradually decreased.The Experimental Study on Adhesion Molecules and GJIC in Mediating Hematogenou...