Cell Phenotype Determines PAI1 Antiproliferative Effect—Suppressed Proliferation of the Lung Cancer but Not Prostate Cancer Cells

Abstract

Plasminogen inhibitor activator type 1 (PAI-1) is an important regulator of tumor growth and metastasis formation acting directly via specific urokinase complexing or indirectly due to its affinity to vitronectin. We have shown previously that PAI-1 modifies angiogenic activity of endothelial cells in a dose-dependent manner but also in close relationship to the cell phenotype. Present study aimed on evaluating the PAI-1 effect on the proliferative activity of lung cancer cells (A549), prostate cancer cells (DU145) as well as endothelial cells (HUVEC). Mutated PAI-1 (1, 10, 100 microg/mL) characterized by the prolonged antifibrinolytic activity (T1/2 approximately 7000 h) inhibited proliferation of lung cancer A549 cells in a dose-dependent (p < 0.001) and time-dependent (p < 0.001) manner. No significant effect on the DU145 prostate cancer cells has been observed except of the 72 h cultures with highest PAI-1 concentration (100 microg/ml) (p < 0.001). Proliferative activity of endothelial cells (HUVEC) was affected by 100 microg/ml PAI-1 only, and independent of the culture period (24, 48 and 72 h, p < 0.001). Plasminogen inhibitor activator type 1 modulates cell proliferation via antifibrynolitic mechanizm time- and dose-dependently, however final outcome is strongly affected by the cell phenotype.