Hyperthermia enhances the cytotoxicity of National Institutes of Health 3T3 cells transfected with a noncleavable transmembrane pro-tumor necrosis factor deletion mutant.
Hyperthermia has been shown to potentiate the cytotoxicity of exogenously added tumor necrosis factor (TNF) against tumor cell targets. The mechanism for that interaction is not known, but among the possibilities are that heat enhances internalization of ligand-bound TNF or enhances processing of internalized TNF. In this study, we found that NIH 3T3 cells transfected with an expression vector containing the full-length human pro-TNF secreted TNF and that hyperthermic treatment of chromium-labeled L929 target cells at 43 degrees C for 1 h potentiated the cytotoxicity of these transfectants against the L929 cells in clonogenic survival and chromium-release assays. On the other hand, transfectants expressing a transmembrane, nonsecretable pro-TNF mutant that kills L929 cells by cell-to-cell contact without internalization also exhibited enhanced cytotoxicity against heated L929 cell targets. Thus, potentiation of the cytotoxicity of TNF by hyperthermia is not strictly dependent on enhanced internalization of ligand-bound TNF or enhanced processing of internalized TNF.
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
S P
SP
Tomasovic
M
M
Khodadadian
M C
MC
Hung
J
J
Klostergaard
D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D015316:Genetic Therapy; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D051379:Mice; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha