Collagen required for proliferation of cultured connective tissue cells but not their transformed counterparts

THE proline analogue, cis -hydroxyproline, when incorporated into collagen, prevents collagen secretion 1 and also inhibits the growth of fibroblasts in vitro 2 . We describe here studies on the mechanism of action of cis -hydroxyproline on cell proliferation of primary cultures of murine connective tissue cells and of their spontaneously transformed, tumorigenic counterparts. We find that the analogue inhibits the attachment, spreading and proliferation of the connective tissue cells and that these effects are completely reversed when the cells are grown on collagen-coated dishes. The tumorigenic cells are less affected by cis -hydroxyproline even though their collagen synthesis is inhibited to a similar extent to the connective tissue cells. These results suggest that the presence of a collagen matrix is required for the growth of some connective tissue cells in vitro but not for the growth of their tumorigenic counterpart.