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Regulation of the Urokinase-Type Plasminogen Activator System in Mammalian Cell Lines

The urokinase-type plasminogen activator system consists of urokinase plasminogen activator (uPA), urokinase type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). The main role of urokinase is the conversion of plasminogen to plasmin, extracellular protease involved in the degradation of extracellular matrix. uPA system has a role in a number of physiological processes, as well as in the metastatic processes. The aim of the study was to compare the urokinase activity and its regulation in different cell lines, under basal conditions and after treatment with several chemotherapeutical agents. Glioblastoma A1235 cells increased the uPA activity after treatment with alkylating agent, retinoic acid and sodium salicylate. Breast cancer cells MDA-MB-231 downregulated urokinase activity after sodium salicylate treatment and increased after treatment with retinoic acid, as well as fibroblast cell line. Dynamin inhibitor inhibited the urokinase activity of A1235 and MDA-MB-231 cells. HEK-293 cells did not change uPA activity after different treatments. In conclusion, the uPA system mechanisms and its regulation are cell-type specific.

urokinase, plasminogen activator inhibitor-1, dynamin inhibitor, mammalian cell lines, regulation

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