Transforming growth factor-β (TGFβ) is a regulator of cellular proliferation which can alter the proteolytic activity of cultured cells by enhancing the secretion of endothelial type plasminogen activator inhibitor and affecting the secretion of plasminogen activators (PAs) in cultured fibroblastic cells. We used the TGFβ-responsive malignant human lung adenocarcinoma cell line A549 to study the relationships between the known TGFβ-induced growth inhibition and the effects of TGFβ on the secretion of PA activity by A549 cells. PA activity was quantitated by caseinolysis assays, and characterized by urokinase mRNA analysis, immunoprecipitation, and zymography assays. PA-inhibitor production was observed in autoradiograms of SDS-polyacrylamide gels and reverse zymography assays. It was found that TGFβ enhanced the production of PA activity by these cells, in accordance with an enhancement of urokinase mRNA levels. A concomitant stimulation of type 1 PA-inhibitor production was also observed in A549 cells in response to TGFβ. In contrast to the observations of A549 cells, TGFβ caused a decrease in the expression of both urokinase and the tissue-type PA mRNA in human embryonic WI-38 lung fibroblasts indicating opposite regulation of the expression of PAs in these cells. The results suggest that TGFβ may play a role in the regulation of the invasive, proteolytically active phenotype of certain lung carcinoma cells.
ASJC Scopus subject areas
- Cell Biology