Tumor necrosis factor stimulates ornithine decarboxylase activity in human fibroblasts and tumor target cells

✍ Scribed by Dr. Nicholas J. Donato; Judy Rotbein; Michael G. Rosenblum

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 834 KB
• Volume: 46
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240460111

✦ Synopsis

The activity of the polyamine biosynthetic enzyme, ornithine decarboxylase (ODC), has been shown to be rapidly modulated by a variety of growth regulatory molecules. In this report the effect of the growth modulatory peptide, tumor necrosis factor, on ODC activity was examined on two cell lines which express equivalent TNF binding properties, but differ in their growth response when exposed to this factor. TNF treatment of WI-38 fibroblasts stimulated both their growth and induced ODC activity 5-1 0-fold when measured 6-24 h after TNF incubation. TNF induced cytotoxicity in ME-I 80 cervical carcinoma cells and, interestingly, stimulated both ODC activity (3-6-fold) and putrescine accumulation when measured prior to the onset of cytotoxicity. Induction of ODC was TNF concentrationdependent and paralleled the concentration-dependency for cytotoxicity. Based upon studies with cycloheximide, de novo protein biosynthesis was required for TNF-mediated ODC induction in ME-1 80 cells.

The effects of other growth inhibitory peptides and growth factors were analyzed for their combined effect on ODC activity in TNF-treated or untreated ME-1 80 cells. Interferon gamma treatment had no significant effect on basal ODC activity but inhibited TNF-mediated ODC induction by -50%. EGF treatment resulted in a potent stimulation of ODC activity which was not effected by TNF pre-treatment or coadrninistration on ME-1 80 cells. These results suggest that TNF has properties which are similar to those of a growth factor and distinct from those of other growth inhibitory peptides. The early growth factor-like actions of TNF occur on both normal fibroblasts and some tumor cells and evidence suggests that these effects are antagonistic to the antiproliferative effects of TNF.