Synergistic action between tumor necrosis factor-alpha and transforming growth factor type-beta: consequences for natural antitumor mechanisms.
TNF-alpha and TGF-beta are central signal molecules for natural antitumor mechanisms. Our data demonstrated that both factors act synergistically during apoptosis induction in transformed cells. This interaction of the two factors may have biological consequences for the efficiency of natural antitumor systems: 1) Transformed cells pretreated with TNF-alpha could be eliminated more efficiently by neighbouring nontransformed cells during intercellular induction of apoptosis; 2) TGF-beta pretreatment of transformed cells night sensitize them for apoptosis induction by macrophages. These findings allow three major conclusions: 1) Endogenous survival factors seem to be central regulatory elements for different apoptosis-inducing systems: 2) Macrophages and intercellular induction of apoptosis should be able to act in a synergistic way during the control of oncogenesis; 3) Resistance against one of the two mechanisms might cause resistance against the other as well.
Schulz
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A
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene Universität Freiburg, D-79104 Freiburg, Germany.
Bauer
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G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide