DISPASE-MEDIATED BASAL DETACHMENT OF CULTURED KERATINOCYTES INDUCES UROKINASE-TYPE PLASMINOGEN-ACTIVATOR (UPA) AND ITS RECEPTOR (UPA-R, CD87)

Keratinocytes synthesize and secrete urokinase-type plasminogen activa tor (uPA), which is bound in an autocrine manner to a specific recepto r (uPA-R, CD87) at their surface. Plasminogen, which is also bound to membrane binding sites, is readily activated by uPA-R-bound uPA. Thus, plasmin for proteolysis of pericullular glycoproteins is provided. Wh ile uPA-R and uPA are at low to undetectable levels in keratinocytes o f the normal epidermis, both compounds are upregulated in migrating ke ratinocytes during reepithelialization of epidermal defects and in aff ected keratinocytes of various epidermal disorders, including bullous dermatoses. We have hypothesized that the disturbance of cell/matrix i nteractions-a common feature of these diverse pathological situations- induces uPA/uPA-R. Accordingly, we explored whether the dispase-mediat ed detachment of cultured keratinocytes, which have formed a multilaye red epidermis-like structure in vitro, induced uPA and uPA-R. We found increases in uPA secretion, cell-associated uPA activity, and uPA- an d uPA-R-antigen in keratinocytes upon dispase-mediated detachment from their growth substratum. The increase was preceded by an increase in uPA-R- and uPA-specific mRNA, which was not observed when the proteina se inhibitor phosphoramidon was added together with dispase. In conclu sion, we present evidence that experimental detachment with dispase pr ovides signals for the concomitant upregulation of uPA-R and uPA. The findings support the hypothesis that cell/matrix interactions may infl uence the expression of the cell surface-associated PA system in human keratinocytes. (C) 1996 Academic Press, Inc.