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

肾细胞癌及其转移亚系的建立及转移机制的研究

基本信息

批准号：
01570897
负责人：
TSUKAMOTO Taiji
金额：
$ 1.47万
依托单位：
Sapporo Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570897/
关键词：
mouse renal adenocarcinoma highly metastatic line in vitro invasiveness type IV collagenolytic activity growth factors suppression of lung metastasis cytokines マウス賢腺癌転移株臓器親和性 Type IV collagenolysis 腎細胞癌 in vitro invasion assay

项目摘要

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.

我们从链脲佐菌素化学致癌的小鼠肾腺癌中筛选出高转移性的亚系，这些亚系的体外侵袭能力高于其亲本，表明体外侵袭能力与体内转移能力平行。这些细胞系还显示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需要的。在人肾细胞癌的体外侵袭研究中，同一患者转移灶来源的细胞比原发灶来源的细胞具有更强的侵袭能力。使用这两个细胞系，我们确定，在体外侵袭性是非常密切相关的IV型胶原溶解活性的细胞系。结果表明，IV型胶原溶解活性在一定程度上调节了体外侵袭潜力。上述人肾细胞癌细胞的体外侵袭能力受EGF和TGF β 1的影响。EGF增强细胞侵袭力，TGF-β 1抑制细胞侵袭力。当研究IV型胶原溶解活性时，EGF刺激该活性，但TGF-β 1抑制该活性。因此，这些生长因子对体外侵袭的影响是通过它们对PM IV胶原溶解活性的作用介导的。高肺转移亚系的实验转移被干扰素-γ、白细胞介素-2和LAK治疗抑制，提示这些细胞因子和免疫治疗可能在临床情况中有用。