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A critical attribute of invasive carcinomas is their ability to degrade components of the extracellular matrix, a process achieved by the matrix metalloproteases. In the human squamous cell carcinoma cell line II-4, mRNA and protein expression of the matrix metalloprotease matrilysin was observed to be significantly higher in confluent than in log-phase growth conditions. The purpose of this study was to determine the basis for this switch in constitutive matrilysin expression. Conditioned medium from confluent cultures did not induce matrilysin in log-phase cultures, nor did conditioned medium from log-phase cultures repress matrilysin expression in confluent cultures. Thus, matrilysin expression was found not to be controlled by factors autocrine product. Matrilysin protein levels were, however, found to be directly correlated to the degree of cell-cell contact. Incubation of confluent cultures in 30 microM calcium medium, which disrupts E-cadherin-mediated cell-cell contact, was subsequently found to inhibit matrilysin expression, as did treatment with an anti-E-cadherin-neutralizing antibody. These results demonstrate that the degree of cell-cell contact mediated by the E-cadherin cell-adhesion molecule can influence constitutive metalloprotease expression levels in cultured squamous cell carcinoma cells.

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