PLASMINOGEN ACTIVATORS (t-PA and u-PA) IN HUMAN NEOPLASTIC CELL LINES AND THEIR MODULATION BY BASEMENT MEMBRANE COMPONENTS

Plasminogen activators (PA)may play an important role in the regulation of enzyme activation relative to basement membrane degradation associated with the invasive growth of tumors. In order to acquire a better understanding of the complex cascade reactions leading to the formation of plasmin, we have undertaken a comparative study of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators in cellular extracts of 20 human cancer cell lines (13 malignant melanomas, 6 breast adenocarcinomas and 1 vulvar carcinoma). Four malignant cell lines,showing various t-PA or u-PA activity levels, were selected to study the modulation of proteolytic activity by laminin and fibronectin, major components of basal membrane. This study was performed in cellular extracts and conditioned medium. Our results showed that melanoma cells have high t-PA activity preferentially released into the culture medium. On the vulvar cell line, A 431, u-PA activity predominates and is also secreted into the medium. In contrast, breast cancer cells MCF-7 and MDA show u-PA activity, mostly recovered in the cellular extracts. An enhancement of respective PA activities occurs when cells are cultured on fibronectin or laminin, varying with the nature of the cell line.

Additional studies are needed to precise interrelation between tumor cells, basement membrane components and PA activities and the potential significance of proteolytic activities as markers of malignancy and invasive capacity.