Cytotoxicity Induced by Recombinant Human Tumor Necrosis Factor-α Dependent on the Types of Its Receptors on Canine Cells

Abstract

Based on the recent findings that show how recombinant human tumor necrosis factor (rh-TNF)-α has potent antitumor activity on human cancer patients when it locally administrated, we have tested the cytotoxicity of rh-TNF-α on 3 canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and (3) Mardin Darby canine kidney cells (MDCK). The cell surface expression of TNF-α receptors on these canine cells was also determined with anti-human TNF RI and RII polyclonal antibodies. Our data shows that on CKCa-1 which has TNF RI receptors rh-TNF-α induced cytotoxicity. By contrast, it exhibited no toxicity on canine mastocytoma which has mainly RII receptors. The data also suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the cytotoxicity of rh-TNF-α. Combined with ACT-D, rh-TNF-α showed the cytotoxicity on MDCK which possessed both TNF RI and RII receptors. The results indicate that the cytotoxicity of rh-TNF-α depends on the presence of TNF RI receptors on canine tumor cells.