Human cancer cells have specifically lost the ability to induce the synergistic state caused by tumor necrosis factor plus interferon-beta.
Tumor necrosis factor (TNF) and the members of the interferon (IFN) family are major inducible cytokines that function to counteract viral infections or cellular transformation. Recently, our lab has characterized a novel antiviral state which is induced in primary human fibroblasts by co-treatment with TNF plus IFNbeta. Here, we demonstrate that this synergistic state is both antiviral and cytostatic for primary human cells. Significantly, we observed that a wide spectrum of transformed human cancer cells have universally lost the ability to induce the TNF/IFNbeta synergistic state, as defined by three separate criteria. We hypothesize that the ability to induce the TNF/IFNbeta synergistic state is a unique feature of primary cells and is incompatible with cellular immortalization and/or transformation.
Bartee
Eric
E
Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1600 SW Archer Road, R4-295, Gainesville, FL 32610, USA.
McFadden
Grant
G
D000998:Antiviral Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054697:Cytostatic Agents / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007700:Kinetics; D009233:Myxoma virus / Q000187:drug effects*; D050504:Oncolytic Viruses / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D000998:Antiviral Agents; D054697:Cytostatic Agents; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta