Stimulation of DNA synthesis by cathepsin D digests of fibronectin

A number of studies over the past decade (reviewed in refs 1-3) have suggested an intimate link between fibronectin, proteolysis and the control of cell proliferation. So far, however, no unequivocal connection has been made. Recent evidence that gelatin-binding fragments of fibronectin enhance morphological cell transformation led to the postulate that the fibronectin molecule harbours latent properties released only on proteolysis. These findings led us to investigate the role of fibronectin fragmentation in the regulation of cell growth in vitro, and we report here that whilst fibronectin is without effect, its cathepsin D digests possess the ability to initiate DNA synthesis in serum-deprived quiescent cultures of normal hamster fibroblasts.