PLASMINOGEN ACTIVATION IN MELANOCYTIC NEOPLASIA

A large body of experimental evidence suggests that plasminogen activa tors provide tumoral cells with efficient means to degrade extracellul ar matrix constituents and thereby facilitate their dissemination to d istant sites. Melanocytic neoplasia encompass a spectrum of lesions ex hibiting diverse clinical behavior that remain difficult to predict wi th current histopathological evaluations. Little information concernin g the contribution of plasminogen activation in diagnostic specimens o f human melanocytic tumors is presently available. We thus analyzed bi opsy specimens of pigmented skin lesions by histological techniques th at identify the cellular sites of synthesis of plasminogen activators and of their inhibitors and that localize the sites of plasminogen act ivators-catalyzed enzymatic activities. We found that urokinase-type p lasminogen activators (uPA) and plasminogen activator inhibitor type 1 mRNAs accumulate in atypical nevocytes and in melanoma cells, but not in benign nevocytes. However, uPA-catalyzed proteolytic activity was detected exclusively in melanomas. These observations suggest that up- regulation of the uPA gene is an early feature of melanocyte transform ation and that unbalanced enzyme/ inhibitor activity is associated wit h the malignant phenotype. By supporting a role for uPA in melanoma in vasiveness, they provide a novel tool for the evaluation of atypia in nevi.