Cell‐cell contact activation of fibroblasts increases the expression of matrix metalloproteinases

Background. We recently found that direct homotypic cell‐cell contacts between human dermal fibroblasts induce a novel form of cell activation leading to non‐apoptotic programmed cell death. As the major features of this process we identified massive induction of cyclo‐oxygenase‐2 and production of inflammatory prostaglandins. On the surface of the decomposing spheroids, activation of the major extracellular proteolytic cascade, plasminogen activation, associated with surface exposure of α‐enolase, took place.Aim. To further characterize pericellular proteolysis by cell‐cell contact‐activated fibroblasts we studied the role of the other major extracellular proteolytic system, matrix metalloproteinases (MMPs).Methods. MMP expression in fibroblast clusters and monolayers was compared using mRNA microarrays and immunoblot analyses. The activities of MMPs were confirmed using MMP inhibitors and caseinolysis.Results. In microarrays MMP‐1, ‐10, and ‐14 (MT1‐MMP) were induced 5.8‐, 106‐, and 5.6‐fold, respective...