TUMOR CELL-DERIVED COLLAGENASE-STIMULATORY FACTOR INCREASES EXPRESSION OF INTERSTITIAL COLLAGENASE, STROMELYSIN, AND 72-KDA GELATINASE

The tumor cell-derived collagenase-stimulatory factor (TCSF) was previ ously purified from human lung carcinoma cells (S. M. Ellis, K. Nabesh ima, and C. Biswas, Cancer Res., 49: 3385-3391, 1989). This protein is present on the surface of several types of human tumor cells in vitro and in vivo and stimulates production of interstitial collagenase in human fibroblasts. In this study it is shown that TCSF stimulates expr ession in human fibroblasts of mRNA for stromelysin 1 and 72-kDa gelat inase/type IV collagenase, as well as for interstitial collagenase. Me asurement of enzyme protein by immunoassay showed that the amounts of interstitial collagenase and stromelysin 1 were increased in TCSF-trea ted fibroblasts; gelatin zymography indicated that there was an increa se in the 72-kDa gelatinase. These results indicate that tumor cell in teraction with fibroblasts via TCSF could lead to increased degradatio n of interstitial or basement membrane matrix components and thus to e nhanced tumor cell invasion.