Microenviroment and organ specific metastases in urological cancers as tools to elucidate molecular mechanism of carcinogenesis and tumor development.

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Ninety-seven primary(renal cell carcinomas) RCCs were analyzed for the protein expression of Snail, Slug, MMP2 and MMP9 by immunohistochemistry. Snail protein expression level was positively correlated with pathological tumor stage, histological grade and the presence of sarcomatoid carcinoma. Because Snail was positively associated with malignant potential of RCCs, involvement of Snail in the invasiveness of an RCC cell lines 786-O and ACHN were examined in the Matrigel invasion assay by down-regulating the gene expression with small interfering RNA(siRNA). Invasion of the cells through Matrigel in vitro was inhibited under this condition. Furthermore, expression levels of MMP2 and MMP9 were positively correlated with pathological tumor stage and the presence of sarcomatoid carcinoma. In conclusion, these data suggest that Snail has an important role in invasion and metastasis, and that silencing the gene may be a potenal therapeutic target in RCCs.Receptor activator of NF-κB ligand(RANKL) and its receptor, receptor activator of NF-κB(RANK), play a key role in osteoclastogenesis RANKL protein expression level showed positive correlations with the primary tumour stage and distant metastasis. RANKL and RANK expression was observed in metastatic RCCs in the bone and other organs, suggesting that they play a role in metastasis to the bone and other organs. Recombinant RANKL protein stimulated migration of a clear cell RCC cell line, Caki-1, in vitro, and this enhanced migration was inhibited by the administration of recombinant OPG protein. These data suggest that the RANKL-RANK-OPG system is involved not only in the bone metastasis of RCCs but also in metastasis to other organs through the stimulation of cancer cell migration.