1976 Chapters (Layout Features)

PROTEASES PRODUCED BY NORMAL AND MALIGNANT CELLS IN CULTURE

Rifkin, Daniel B.; Pollack, Robert

The production of plasminogen activators (PA) is associated with the neoplastic transformation of many types of cells. A number of the phenotypic changes associated with transformation are dependent, at least in part, upon the generation of plasmin by the PA secreted by these cells. One of these changes, the loss of intra­ cellular actin-containing cables in neoplastic cells, can be correlated with the level of extracellular proteases. Moreover, these same proteases can cause the disappear­ ance of actin-containing cables in normal cells when sup­ plied exogenously. Therefore, plasmin acting from the external side of the plasma membrane appears to be cap­ able of causing the dissolution of these intracellular structures, The control of PA synthesis in two cell types, chick embryo fibroblasts infected with a temper­ ature-sensitive mutant of Rous sarcoma virus and human embryonic lung cells, has been examined. Induction of PA requires both RNA and protein synthesis. Deinduction of PA also requires a new RNA and, perhaps, protein to be made. If the synthesis of this RNA is inhibited, PA pro­ duction can continue for many hours under conditions that are normally non-pemissive.