engleski

Sodium salicylate modulation of urokinase plasminogen activation system in breast cancer cells

Urokinase plasminogen activation system is a precisely regulated system important for controlled proteolysis of extracellular matrix. It is involved in various physiological and developmental processes, as well as in invasive growth of tumors and metastasis. The system consists of extracellular protease, urokinase plasminogen activator (uPA), its inhibitors PAI-1 and PAI-2 and specific cell receptor, uPAR, involved in localized proteolysis. In this study we investigated the effect of sodium salicylate (NaS) on the plasminogen activation system of MDA MB-231 human breast cancer cell line. These cells produce high levels of extracellular uPA and we observed that NaS decreased uPA activity in time and concentration-dependent manner. Analysis of gene expression showed no significant change in the expression of uPA, PAI-1 and uPAR in these conditions indicating the role of extracellular uPA activity inhibition. In order to elucidate the signaling mechanisms influenced by NaS modulation of uPA system, we also analyzed expression of IkB and β-catenin. While the expression of β-catenin, involved in PI3K pathways, remained unchanged, slight increase in NFkB activity was indicated. Cells treated with NaS changed their morphology. As these features could be connected with focal adhesion, we analyzed integrin gene expression. Further investigations are needed to elucidate the possible implementation of sodium salicylate in invasive tumor growth inhibition.

urokinase ; plasminogen activator ; salicylate

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