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Study on treatment for prevention of metastasis in renal cell carcinoma

肾细胞癌预防转移的治疗研究

基本信息

批准号：
04454406
负责人：
TSUKAMOTO Taiji
金额：
$ 2.05万
依托单位：
Sapporo Medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454406/
关键词：
renal cell carcinoma metastasis prevention tetracyline type IV collagenolysis adhesion molecules cytokines マウス腎腺癌肺転移血管新生阻害血管内皮細胞 in vitro浸潤能 VCAM-1 VLA-4 浸潤転移 type IV1111111111111111111 collagenolysis

项目摘要

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.

在这项研究中，我们揭示了肾细胞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肺转移的抑制作用。体外研究表明，米诺环素的这种抑制作用是通过抑制小鼠肾腺癌细胞的IV型胶原溶解而实现的。结果表明，具有这种效果的药物将在临床上适用于肾细胞癌转移预防治疗。我们正在努力积累临床结果。2)IFN-γ和IL-2对小鼠腺癌的实验性转移有抑制作用。虽然这两种细胞因子抑制生长的皮下接种腺癌，IFN-γ也抑制IV型胶原溶解的腺癌细胞，这表明这种抑制作用参与减少肺转移结节的数量。3)利用体外侵袭实验，我们发现炎症细胞因子（IL-6，IL-1和TNF）增强了人肾癌细胞的体外侵袭能力。这些细胞因子增加了内皮上VCAM-1的表达，这导致这些细胞因子增强了内皮之间的粘附，并且表达VLA-4（VCAM-1的配体）的肾细胞癌细胞参与了癌细胞侵袭性的增强。