INDUCTION OF MEMBRANE-TYPE MATRIX METALLOPROTEINASE-1 (MT1-MMP) EXPRESSION IN HUMAN FIBROBLASTS BY BREAST ADENOCARCINOMA CELLS

Membrane-type matrix metalloproteinase 1 (MT1-MMP) has been recently d escribed as an activator of proMMP-2 (MMP-2) which is involved in tumo r invasion, We have shown by in situ hybridization that MT1-MMP is pro duced by stromal cells in close contact to preinvasive and invasive tu mor cells of breast carcinomas. Of particular interest,vas the observa tion that some fibroblasts express this enzyme in focal areas in prein vasive lesions, suggesting that particular tumor cells may stimulate f ibroblasts to produce MT1-MMP, We have therefore compared the ability of two different breast cancer cell lines, one non-invasive (MCF7) and one invasive (MDA-MB-231) to stimulate MT1-MMP production in human fi broblasts with consequent proMMP-2-activation. The MDA-MB-231 conditio ned medium induced MT1-MMP mRNAs in human fibroblasts and a parallel a ctivation of proMMP-2 whereas MCF7 conditioned medium did not have any effect, These results suggest the existence of soluble factor(s) secr eted by invasive or some preinvasive breast tumor cells which stimulat e fibroblasts to produce and activate MMPs, and emphasize the cooperat ion between cancer and stromal cells in tumor invasion.