PROLIDASE IN HUMAN BREAST-CANCER MCF-7 CELLS

Prolidase (EC 3.4.13.9) is an ubiquitously distributed imidodipeptidas e that catalyzes the hydrolysis of dipeptides containing C-terminal pr oline or hydroxyproline. The enzyme plays an important role in the rec ycling of proline for collagen synthesis and cell growth. We have show n previously that prolidase activity in normal human skin fibroblasts is regulated by the interaction of type I collagen with beta(1) integr in receptor. In the present study, we investigate prolidase activity i n MCF-7 cells and find it is only one-third of that in normal human sk in fibroblasts. The relative difference in prolidase activity is corro borated by enzyme protein with Western immunoblot analysis. We propose that the decrease in prolidase activity is due to derangement of regu lation by the collagen-beta(1) integrin receptor axis. Supporting evid ence comes from the following observations: (1) relative collagen cont ent elaborated by MCF-7 cells as compared to fibroblasts is lower by 3 0% in sparse cells and by 80% at confluence; (2) collagenase treatment of both cell types results in decreased enzyme activity; (3) in contr ast to fibroblasts, prolidase activity in MCF-7 cells is not stimulate d by the addition of type I collagen or beta(1) integrin antibodies (a gonist for beta(1) integrin receptor); and (4) in contrast to fibrobla sts, MCF-7 cells express only trace amounts of beta(1) integrin recept or as shown by Western immunoblot analysis. Thus, we conclude that dep ressed prolidase activity in MCF-7 cells may be a result of disturbanc es in signaling mediated by beta(1) integrin-collagen interaction. (C) 1998 Elsevier Science Ireland Ltd.