Enhancement of neutral metalloproteinase in the dermis after one topical application of tumor-promoting phorbol ester.

The effect of a tumor-promoting skin mitogen, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the induction of matrix degradation in the dermis of mouse skin has been examined. Dermis specimens were analyzed for proteoglycan content and neutral proteoglycan degrading activity. Total neutral metalloproteinase activity (latent plus active forms), determined by direct tissue assay, was significantly elevated in TPA-treated dermis than in control dermis. The active form of neutral metalloproteinase was significantly higher in TPA-treated dermis than in control dermis. Serine protease activity on proteoglycans was much lower than that of metalloproteinase. The increase in the total and active neutral metalloproteinase supports the hypothesis that these enzymes are involved in matrix degradation which is related to tumor promotion.