INDUCTION OF FIBROBLAST GELATINASE-B EXPRESSION BY DIRECT-CONTACT WITH CELL-LINES DERIVED FROM PRIMARY TUMOR BUT NOT FROM METASTASES

During cancer progression, tumor cells interact with stromal cells. As a consequence, matrix metalloproteinases are produced that contribute to the degradation of the extracellular matrix. This study used cocul ture systems to investigate fibroblast interaction with three colon ca ncer cell lines isolated from a single patient. Cells from primary col orectal carcinoma, but not from corresponding liver or lymph node meta stases, induced gelatinase B expression by fibroblasts of different ti ssue origin. Remarkably, direct cell-cell contact was required for thi s induction, which occurred at the pretranslational level (as revealed by Northern blot analysis) and was completely blocked by anti-beta 1 integrin. monoclonal antibody, but only partially blocked by anti-alph a 5 or anti-alpha v. Induction was also inhibited by cytochalasin D, s taurosporine, or dexamethasone, suggesting the need, respectively, for an organized actin cytoskeleton, protein kinase C, and AP-1-driven ge ne transcription. Our data suggest that direct tumor-stromal cell cont act is one inductive event involved in matrix metalloproteinase expres sion by stromal cells.