CRANIAL NEURAL CREST CELLS SYNTHESIZE AND SECRETE A LATENT FORM OF TRANSFORMING GROWTH-FACTOR-BETA THAT CAN BE ACTIVATED BY NEURAL CREST CELL PROTEOLYSIS

Transforming growth factor β (TGF-β) is an important regulator of cell growth and differentiation. TGF-β is usually secreted in a latent form (i.e., not biologically active) that can be activated by limited exposure to low pH or specific proteolytic cleavage. In this study, we (1) assayed cranial neural crest (NC) cell-conditioned medium for the presence of active and latent TGF-β, (2) determined whether TGF-β was activated by NC-generated plasmin, and (3) examined whether active TGF-β1 regulates NC cell plasminogen activator activity. Results show that under serum-free conditions, essentially all of the TGF-β secreted by NC cells is in a latent form. However, 24 hr after adding plasminogen to the cultures, active TGF-β was detectable. Treatment of NC cells with active TGF-β1 significantly decreased NC cell plasminogen activator activity. These data suggest that NC cells secrete a latent form of TGF-β that can be activated under conditions favoring the generation of local proteolytic activity and that levels of plasminogen activator activity may be autoregulated via an autocrine effect of this growth factor. © 1993 by Academic Press, Inc.