VINBLASTINE-DEPENDENT DOWN-MODULATION OF TNF RECEPTORS IN HUMAN OSTEOSARCOMA CELLS IS MEDIATED BY PROTEIN-KINASE-C ACTIVITY

The binding of tumor necrosis factor (TNF) to a human osteogenic sarco ma cell line (Saos-2) was investigated. These cells express two types of receptors as determined by specific monoclonal antibodies. Vinblast ine induced a down-modulation of these receptors weaker than the one p roduced by phorbol esters or okadaic acid treatment. On exposure of ce lls to 10 mu M vinblastine for two hours an approximately 55-65% dimin ution of TNF binding was observed, but only 20% reduction occurred und er long-term vinblastine treatment. TNF receptor down-modulation induc ed by vinblastine was partially prevented by protein kinase C inhibito rs or protein kinase C depletion. It is suggested that the regulation of TNF binding to each one of its receptors in Saos-2 cells always occ urs in a phosphorylation-dependent manner. (C) 1994 Academic Press, In c.