Regulation of the TNF-α Receptor in Human Osteosarcoma Cells: Role of Microtubules and of Protein Kinase C

The effect of the tumor promoter 4β-phorbol 12-myristate 13-acetate and of the phosphatases inhibitor okadaic acid on the binding of tumor necrosis factor-α (TNFα) to a human osteogenic sarcoma cell line (Saos-2) was investigated. Both substances prevented almost completely TNF binding to its receptors. The effect of 4β-phorbol 12-myristate 13-acetate was reversed by the protein kinase C inhibitors staurosporine and caiphostin C or by protein kinase C depletion. Vinblastine, under conditions causing full microtubule disassembly, produced only a 50% decrease of TNF binding. Viablastine plus PMA was additive in fully preventing TNF binding. It is suggested that the degree of binding of TNF-α to its receptors in Saos-2 cells is under the control of a microtubule-dependent and of a microtubule-independent regulatory pathway.