Enhanced migration of tumor cells in response to collagen degradation products and tumor cell collagenolytic activity.

The migration of ascites and cultured hepatoma cells, AH109A of rat (Donryu) origin and MH134 of mouse (C3H), was enhanced by collagen degradation products (CDP) in vitro using the modified Boyden chamber, but not by collagen. Both tumor cells demonstrated somewhat increased motility in the presence of CDP regardless of whether or not there was a gradient present, but the maximum response was seen in the presence of a gradient. MH134 cells responded more effectively to CDP than AH109A cells and showed similar migratory responses to type I and IV collagen degradation products (CDP-I and -IV). Synthetic di- or tripeptides containing hydroxyproline were less chemotactic for MH134 cells than CDP-I and -IV. Both proteases (collagenase and trypsin) and MH134 cells could degrade a collagen substrate and generate CDP. These findings suggest that CDP released during the process of invasion may play a role in the migration of tumor cells and consequent formation of metastases.