INDUCTION OF MATRIX METALLOPROTEINASE-9 EXPRESSION IN BREAST-CARCINOMA CELLS BY A SOLUBLE FACTOR FROM FIBROBLASTS

Tumor-stromal interactions appear to play an important role in the ind uction of metalloproteinase expression in malignant tumors. We describ e a tissue culture system in which expression of MMP-9 (gelatinase B o r the 92 kDa type IV collagenase/gelatinase) was induced by co-cultiva tion of fibroblasts with breast cancer cell lines. While neither the b reast cancer cells nor the normal rat embryo fibroblasts made MMP-9 al one in culture, human MMP-9 was made in the co-cultures. The MMP-9 was secreted in a latent form. The induction occurred at least in part th rough increases in the MMP-9 mRNA levels in the breast cancer cells. T hese increases did not appear to require protein synthesis. Conditione d medium from the fibroblasts could duplicate the induction of MMP-9 i n the breast cancer cell lines. The active factor in the medium was in activated by heat or by trypsin suggesting that it was a protein. This protein was in the size range of 30-100 kDa. Thus, fibroblasts could secrete a factor which was able to regulate the expression of MMP-9 in breast cancer cells.