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Interaction if Cell Adhesion Molecules and Tumor Cells on the Production of Matrix Metalloprotease in Gynecological Cancers

细胞粘附分子和肿瘤细胞对妇科癌症基质金属蛋白酶产生的相互作用

基本信息

批准号：
06671662
负责人：
SAITO Toshiaki
金额：
$ 1.34万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

We have investigated the interaction of extracellular integrin ligands and tumor cells on the invasion of gynecological cancer cells.1.An in vitro invasion assay was used as the model system to study the effect of 3T3 fibroblast conditioned medium (FCM), human uterine fibroblasts conditioned medium (HUFCM), purified human fibronection and laminin on the invasion of cervical carcinoma cells. The 3T3 FCM and HUFCM significantly enhanced the invasion of a cervical carcinoma cell lines, HeLa, SiSo, CAC-1 and TMCC.This enhancement of invasion was inhibited by anti-fibronectin antibody. Purified fibronectin, laminin alone enhanced the invasion in a dose-dependent anner for all cell lines. The pretreatment of cells with cell binding aminossequences, GRGDSP and/or YIGSR blocked the enhancement of cell invasion.2.Pretreatment of 3T3 fibroblasts and human uterine fibroblasts by TGF-beta ascorbic acid significantly enhanced the invasion of cervical cancer cells. This treatment also enhanced the production of fibronectin by fibroblasts.3.Usng the zymogram assay, MMP-2 expression of ovarican cancer cells and cervical cancer cells were evaluated. One of the 2 cell lines of ovarian cancer cells and HeLa cells expressed 62kD matrix. metalloproteinase. Both of in vivo cisplatin resistant cell strains aquired the MMP-2 expression. The expression of MMP-2 of HeLa was enhanced by addition of fibronectin in the culture medium.4.Consequently, gynecolgic cancer cells may induce the enhanced production of fibronectin in surrounding stromal fibroblasts. Cellular fibronectin can induce or enhance the invasion of cancer cells by enhancement of the expression of MMP-2 by tumor cells.

本研究探讨了整合素配体与肿瘤细胞的相互作用对妇科肿瘤细胞侵袭力的影响。1.以体外侵袭实验为模型，研究了3 T3成纤维细胞条件培养液（FCM）、人子宫成纤维细胞条件培养液（HUFCM）、纯化人纤连蛋白（FN）和层粘连蛋白（LN）对宫颈癌细胞侵袭力的影响。3 T3 FCM和HUFCM能显著增强宫颈癌细胞系HeLa、SiSo、CAC-1和TMCC的侵袭能力，这种增强作用可被抗纤连蛋白抗体所抑制。纯化的纤连蛋白、层粘连蛋白单独对所有细胞株的侵袭均呈剂量依赖性增强。用细胞结合氨基酸序列、GRGDSP和/或YIGSR预处理细胞可阻断3 T3成纤维细胞和人子宫成纤维细胞的侵袭增强作用。3.采用酶谱分析法检测MMP-2在卵巢癌细胞和宫颈癌细胞中的表达。卵巢癌细胞系和HeLa细胞系中有1株表达62 kD基质。金属蛋白酶两种顺铂耐药细胞株均获得了MMP-2的表达。培养液中加入纤连蛋白可促进HeLa细胞MMP-2的表达。4.妇科癌细胞可诱导周围间质成纤维细胞纤连蛋白的表达增加。细胞纤连蛋白可通过增强肿瘤细胞MMP-2的表达而诱导或增强肿瘤细胞的侵袭。