Pentoxifylline enhances lung colonization and alters cell adhesion and glycosaminoglycan synthesis by metastatic B16 melanoma cells

Abstract

The effect of pentoxifylline on B16 melanoma cell lung colonization, synthesis and properties of glycosaminoglycans (GAGS), and adhesion to and degradation of subendothelial extracellular matrix was examined. Pentoxifylline inhibited cell growth, cell numbers being reduced by 50% following incubation for 4 days in the presence of 250 micrograms/ml pentoxifylline, while the treated cells appeared more flattened, possessed numerous but short dendritic processes, and exhibited greatly enhanced tyrosinase activity and melanin synthesis. Pentoxifylline treatment increased the cells' ability to colonize the lungs of syngeneic C57BL mice following tail-vein injection of 10(5) cells. The number of lung tumours increased from 16.7 +/- 6.1 to 52.2 +/- 17.8. In addition, pentoxifylline-treated cell GAG synthesis was reduced by 36%, and the charge density of chondroitin sulphate reduced, while tumour-cell aggregation and adhesion to subendothelial extracellular matrix was increased, as was the tumour-cell-mediated release of 35SO4 from radiolabelled subendothelial matrix. The observed changes in GAG synthesis may contribute toward the increased cell adhesiveness which, in addition to increased degradation of certain components of the subendothelial extracellular matrix, may account, at least in part, for the enhancement of lung colonization.