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

我们从链脲佐菌素-化学致癌的小鼠肾腺癌中筛选出了高转移的亚系，这些亚系显示出比亲本更高的体外侵袭能力，提示体外侵袭实验揭示的体外侵袭能力与体内转移能力相一致。这些细胞系还具有自发转移潜能和更特异的器官亲和力，这两者都是作为自发选择的转移亚系所必需的。在对人肾细胞癌体外侵袭的研究中，来自转移灶的细胞HNE比来自同一患者原发灶的HNE具有更大的侵袭潜能。利用这两个细胞系，我们发现体外侵袭能力与细胞系的IV型胶原酶活性密切相关。结果表明，IV型胶原酶活性部分调节体外侵袭潜能。上述人肾癌细胞株的体外侵袭能力受EGF和TGFBETA1的影响。EGF增强侵袭性，而TGF-BETA1抑制侵袭性。当检测IV型胶原溶解活性时，EGF刺激其活性，而转化生长因子-β1则抑制其活性。因此，这些生长因子对体外侵袭的影响可能是通过它们对PM IV细胞的溶解活性来实现的。干扰素-γ、白介素2和LAK治疗可抑制高转移性肺转移亚系的实验性转移，提示这些细胞因子和免疫治疗可能在临床上有一定的应用价值。

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.