Pentoxifylline Inhibits Integrin-Mediated Adherence of 12(S)-HETE and TNFα-Activated B16F10 Cells to Fibronectin and Endothelial Cells

Abstract

Background: Pentoxifylline (PTX), a phosphodiesterase inhibitor, inhibits homing of metastatic B16F10 melanoma cells to the lung. Studies on the mechanism of action of PTX showed inhibition of adhesion of cultured melanoma cells to various extracellular matrix substrates and inhibition of cell surface integrin expression. The aim of this study was to determine the effect of PTX on surface expression of integrin and integrin-mediated adhesion induced by biological mediators, tumour necrosis factor (TNF) α and 12(S)-hydroxyeicosatetraenoic acid (HETE), in B16F10 cells. Materials and Methods: B16F10 cells were treated with 12(S)-HETE (1 µM, 1 h), TNFα (5 ng/ml, 2 h) and phorbol 12-myristate 13-acetate (400 nM, 20 min), and the effect of PTX on these treatments was studied by flow cytometry, adhesion assay and confocal microscopy. Results: 12(S)-HETE and TNFα brought about an increase in the surface expression of β₁ integrins and F10 cell adhesion to fibronectin and endothelial cells; this increased adhesion was mediated at least in part by alterations in the localization of β₁ integrins. Pretreatment with PTX was able to completely abrogate this induction in integrin expression. Conclusion: PTX can inhibit surface expression of integrin and integrin-mediated adhesion induced by several biological mediators, and this might be a possible mechanism for its antimetastatic action, in vivo.