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

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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.