Study on treatment for prevention of metastasis in renal cell carcinoma

在这项研究中，我们揭示了肾癌转移的几个重要方面，如下所述。1)四环素衍生物米诺环素对小鼠肾腺癌高转移亚系的实验性肺转移有抑制作用。体外研究表明，米诺环素对小鼠肾腺癌细胞IV型胶原酶的抑制作用来源于其对细胞的抑制作用。提示该药具有预防肾癌转移的临床应用价值。我们现在正在努力积累临床结果。2)干扰素-g和IL-2对小鼠腺癌细胞的实验性转移有抑制作用。虽然两种细胞因子都抑制皮下接种的腺癌的生长，但干扰素-g也抑制了腺癌细胞的IV型胶原分解，提示这种抑制作用参与了减少肺转移结节的数量。3)用培养的人脐静脉内皮细胞和细胞外基质膜系统改良的体外侵袭实验发现，炎性细胞因子(IL-6、IL-1和TNF)增强了人肾癌细胞的体外侵袭能力。这些细胞因子上调内皮细胞VCAM-1的表达，从而增强内皮细胞间的黏附，而表达VCAM-1配体VLA-4的肾癌细胞参与了癌细胞侵袭力的增强。

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.