Molecular analysis of mechanism to metastasis of lung cancer : especially cells motility and growth factor genes

对于癌症患者而言，抑制癌细胞向局部部位的侵袭和转移对预后产生重大影响，成为重要的主题。近年来，有报道称肿瘤生长因子与肿瘤转移的器官选择性有关。本课题组前期从人肺癌细胞中发现了一种与肺癌转移相关的因子--免疫活性细胞刺激物，认为它参与了肺癌转移过程中的细胞运动和肿瘤局部自分泌/旁分泌生长因子的调控，并利用分子生物学方法研究了其产生的生长因子基因作为转移指标的作用。本研究采用17株恶性肿瘤细胞系，其中13株肺癌细胞系，TGF-β mRNA在17株恶性肿瘤细胞系中均有表达。细胞因子IL-8、IL-1 α和IL-6的mRNA表达率分别为80%、65%和35%。我们进一步分析了这些细胞中与肿瘤转移相关的因素。E-cadoherin、CD 44和c-met mRNA分别在13、8和12个细胞系中表达。在10个细胞系中显示了基质胶的逆转活性。这些细胞的逆转活性与基质胶粘附和金属蛋白酶的激活有关，提示多种细胞因子通过微环境中的细胞相互作用对肿瘤的进展起着重要作用。

As for invarsion and metastasis to local site of cancer cells with cancer patients, the inhibition becomes important theme by bringing major influence for prognosis. Recently, the growth factor producced tumor is reported related to the organs selectivity of cancer metastasis by a mouse tumor. Previously, we found a stimulant substance for immuno competent cells with production from human lung cancer cells, the same factor with related to metastasis of lung cancer, we thought that did participate in cell movement to metastasis process of lung cancer and the control of autocrine/paracrine growth factor with tumor local site, then we studied the role in metastasis as an indicator with gene of produced growth factor by molecular biolog. The seventeen cells lines of malignant tumor including 13 lung cancer cells was using.TGF-beta mRNA was expressed in seventeen cells lines of malignant tumor. The mRNA of cytokine IL-8, IL-1alpha and IL-6 was expressed 80%, 65% and 35%, respectively. Further we analyzed for related to tumor metastasis in those cells. E-cadoherin, CD44 and c-met mRNA was expressed in 13 lines, 8 lines and 12 lines, respectively. Inversive activity by matrigel was shown in 10 cell lines. And the inversive activity of those cells related to the adhesion for matrigel and activation of metalloprotinases.Those results suggest the numerous cytokines playd an effective role for tumor progression through the cell interactions in microenvironment.