Growth Factors in the Regulation of Plasminogen-Plasmin System in Tumor Cells

Abstract

Growth regulatory polypeptides, which act in an autocrine or paracrine fashion, are increasingly implicated in the control of pericellular proteolysis. Representatives of major growth factor families, like EGF, PDGF, IGF, FGF, IL, and TGF beta, and in addition, TNFs have effects both on cell proliferation and proteolytic events. Some of them participate in the control of proteolytic events by affecting pericellular PA activity. These factors regulate the synthesis, secretion, and activity of both PAs and their inhibitors in a cell and factor-specific manner. Interestingly, most of these affect simultaneously the secretion of both PAs and their inhibitors, sometimes concomitantly. In addition to PAs, growth factors modulate secretion of collagenases, transin, and stromelysin, and their respective inhibitors, TIMP. The balance of pericellular proteolytic activity is regulated according to the nature and interaction of various growth factors. Pericellular proteolysis can be modulated by growth factors at different levels. Several growth factors are able to regulate the amount and composition of the extracellular matrices. This, in turn, may affect the interactions of certain growth factors with the pericellular matrix structures. Altered structure of the matrix due to excessive proteolytic activity may thus limit the amount and activity of matrix-associated growth factors. Several growth factors exist in latent forms, and activation of these growth factors often requires proteolytic processing. A regulatory loop is thus formed where active growth factors affect the secretion of proteolytic enzymes and thus the concentrations of active ligands.(ABSTRACT TRUNCATED AT 250 WORDS)