Studies on establishment of renal cell carcinoma and its metastatic subline, and on the mechanism of the metastasisl

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We experimentally selected highly metastatic sublines from mouse renal adenocarcinoma developed by streptozotocin-chemical carcinogenesis.These sublines showed higher in vitro invasive potential than their parent line, suggesting that in vitro invasive potential revealed by in vitro invasion assay pararefled in vivo metastatic potential. These lines were also revealed to have spontaneous metastatic potential and more specific organ affinity, both of which are required in as spontaneously selected metastates subline. In the study of in vitro invasion of human renal cell carcinomas, the cell hne derived from the metastatic lesion showed more invasive potential than that from the primary lesion of the same patient. Using these two cell lines, we identified that in vitro invasiveness was very closely correlated with type IV collagenolytic activity of the cell lines. The result suggests that type IV collagenolytic activity regulates, in part, the in vitro invasive potential. The in vitro invasive potential of human renal cell carcinoma cell Ones described above was influenced by EGF and TGFBETA1. EGF enhanced and TGF-BETA1suppressed the invasiveness. When type IV collagenolytic activity was investigated, EGF stimulated the activity, but TGF-BETA1 suppressed it. Thus, the influence of these growth factors on the in vitro invasion was mediated through their action on PM IV conagenolytic activity.Experimental metastasis of highly lung-metastatic sublines was suppressed by interferon-gamma, interleukin-2 and LAK therapy, suggesting that these cytokines and immunotherapy may be useful in clinical situation.