MODULATION OF MATRIX METALLOPROTEINASE-7 (MATRILYSIN) SECRETION IN COCULTURE OF HUMAN COLON-CARCINOMA CELLS WITH FIBROBLASTS FROM ORTHOTOPIC AND ECTOPIC ORGANS

Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix -degrading metalloproteinases that are believed to contribute to the c omplex process of cancer invasion and metastasis. The secretion level of MMP-7 as assayed by immunoblot analysis was low but distinct in the culture medium of a human colon carcinoma cell line, WiDr, whereas no ne of the fibroblasts secreted the detectable level of MMP-7. The cocu lture of WiDr with various human fibroblasts from orthotopic (colon) a nd ectopic (thyroid, brain, lung, and skin) organs significantly stimu lated the secretion of MMP-7 compared with the cultures of individual cells. Reverse transcriptase-polymerase chain reaction analysis and RN A blot analysis suggested that this enhancement occurred at a pretrans lational level. The extent of the stimulation was widely varied by the fibroblasts used and was dependent on the cellular ratios and density in the coculture. There may exist a tendency that fibroblasts of orth ologic origin stimulate more extensively than do those of ectopic orig in. Moreover, in the coculture of high cell density, normal fibroblast s from the ectopic organs reduced the MMP-7 secretion. The stimulation of MMP-7 secretion may be partially mediated through soluble factor(s ); however, direct cell-cell interactions would be required for maximu m stimulation. The enhanced MMP-7 secretion was also observed in cocul ture of colon fibroblasts with other colorectal carcinoma cell lines s uch as RCM-1 and SW837, which secreted hardly detectable levels of MMP -7 in the individual culture. These results suggest that MMP-7 secreti on by colon carcinoma cells is influenced by specific interactions bet ween the carcinoma cells and host fibroblasts.