Study on treatment for prevention of metastasis in renal cell carcinoma

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In this study, we have revealed several important aspects of metastasis in renal cell carcinoma, described below. 1) Minocycline, a tetracycline derivative, inhibited experimental pulmonary metastasis of the highly metastatic subline of murine renal adenocarcinoma. In vitro study indicated that this inhibitory action of minocycline was derived from its suppressive effect on type IV collagenolysis of murine renal adenocaricnoma cells. The result suggests that the drug having such effect would be clinically applicable in the treatment for metastasis prevention in renal cell carcinoma. We are now trying to accumulate the clinical results. 2) INF-g and IL-2 were found to have suppressive effect on experimental metastasis of murine adenocarcinoma. Although both cytokines suppressed growth of the subcutaneously inoculated adenocarcinoma, IFN-g also suppressed type IV collagenolysis of the adenocarcinoma cells, suggesting that this suppressive action participated in reducing number of metastatic nodules of the lung. 3) Using an in vitro invasion assay modified by cultured human umbilical venule endothelial cells and an extracellular matrix membrane system, we found that inflammatory cytokines (IL-6, IL-1 and TNF) enhanced the in vitro invasiveness of human renal cell carcinoma cells. Augmented expression by VCAM-1 on the endothelium by these cytokines, wich resulted in enhancement of adhesion between endothelium by these cytokines, and renal cell carcinoma cells expressing VLA-4 (a ligand of VCAM-1), participated in enhancement of the invasiveness of the carcinoma cells.