摘要：

This chapter describes the protease-mediated morphological changes induced by treatment of transformed chick fibroblast with a tumor promoter. The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus transformed chick embryo fibroblasts (RSVCEF). Concomitant with the PA induction, distinct morphological changes occur in serum-free RSVCEF cultures upon PMA treatment. The morphological changes include enhanced cell clustering and the formation of colonial aggregates of cells. These alterations in the morphology of the PMA-treated transformed cells are inhibited by a number of protease inhibitors including DFP, leupeptin, NPGB, and benzamidine. In a study described in the chapter, a number of protease inhibitors were ineffective in preventing the PMA-induced morphological changes and these included inhibitors of trypsin, chymotrypsin, thrombin, and most importantly, plasmin. The use of a fluorescent substrate to assay PA directly and the use of DFP to label and characterize serine enzymes in the culture fluid from PMA-treated cells indicate that PA is the serine enzyme responsible for the morphological changes.

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