Fibrinolysis associated with oncogenic transformation: morphological correlates

This paper describes some correlations between tumor associated fibrinolysis and the morphological properties of normal and Simian virus 40 (SV40) transformed hamster embryo fibroblast cultures. The rate of fibrinolysis and morphological response are both influenced by the nature of the serum supplement; most sera show an excellent correlation between the rate of fibrinolysis and the development of characteristic morphological changes. Both processes require the presence of the serum factor, plasminogen, and its conversion to plasmin. When normal and transformed fibroblasts are cocultivated under appropriate conditions, the normal cells develop morphological changes similar to those ordinarily expressed by transformed cells. The appearance of these changes in normal cells is also correlated with fibrinolytic activity and the activation of plasminogen. Fibrinolysis and morphological change can be dissociated in media supplemented with sera of bovine origin. When the macromolecular protease inhibitors are destroyed by acid treatment, bovine sera become active in fibrinolysis; however, they do not mediate morphological change, and they can be shown to contain a selective inhibitor of the morphological transformation. These results show that an active fibrinolytic system is a necessary but not a sufficient requirement for morphological changes accompanying transformation of hamster fibroblasts.