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

  • AOKI Mica
    Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University
  • SASAKI Nobuo
    Department of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo
  • NOMURA Koichi
    Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University
  • KATAMOTO Hiromu
    Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University
  • KUBO Kihei
    Department of Radiology, College of Agriculture, Osaka Prefecture University
  • KODAMA Hiroshi
    Department of Veterinary Immunology, College of Agriculture, Osaka Prefecture University
  • MUKAMOTO Masafumi
    Department of Veterinary Immunology, College of Agriculture, Osaka Prefecture University
  • SHIMADA Terumasa
    Veterinary Teaching Hospital, College of Agriculture, Osaka Prefecture University
  • OHASHI Fumihito
    Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University

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.

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