TNF promotes metastasis by impairing natural killer cell activity

Int J Cancer. 1996 May 3;66(3):388-92. doi: 10.1002/(SICI)1097-0215(19960503)66:3<388::AID-IJC20>3.0.CO;2-6.


Inflammatory mediators such as tumor necrosis factor (TNF) and interleukin-1 enhance tumor colony formation in different models of experimental and spontaneous metastasis. The involvement of the natural killer (NK) cell system in this process was investigated. Tumor necrosis factor does not appear to act directly on tumor cells by reducing their susceptibility to the cytotoxic action of NK cells but rather impairs NK activity in tumor-bearing mice. Such impairment of the natural killer system might be one means by which TNF supports tumor colony formation. Even though the metastasis- enhancing effect of TNF remained detectable in mice which have a greatly reduced NK cell cytotoxic activity due to a defect in the bg locus, normal mice which were depleted of NK cells by antibody treatment did not show enhanced metastasis after TNF injection. Therefore, the TNF-enhanced metastasis can only be seen as long as some NK cell function is operating in the animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cytotoxicity, Immunologic / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Fibrosarcoma / immunology
  • Fibrosarcoma / pathology*
  • Immunoglobulin G / pharmacology
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / physiology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred Strains
  • Neoplasm Metastasis*
  • Recombinant Proteins / analysis
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / toxicity
  • Transfection
  • Tumor Necrosis Factor-alpha / toxicity*
  • beta-Galactosidase / analysis
  • beta-Galactosidase / biosynthesis


  • Antibodies
  • Immunoglobulin G
  • Lymphocyte Function-Associated Antigen-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • beta-Galactosidase