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Updated: Jun 23, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Tumor necrosis factor expression in human epithelial tumor cell lines
D R Spriggs1, K Imamura, C Rodriguez
1Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Abstract:
Tumor necrosis factor (TNF) is a monokine with in vitro cytotoxicity for some but not all tumor cells. The basis for sensitivity and resistance to the antitumor effects of this agent remains unclear. The present studies have monitored the effects of TNF on 14 epithelial tumor cell lines. Eleven of these cell lines were resistant to the growth inhibitory effects of TNF (50% inhibitory concentration greater than 1,000 U/ml). 12 of the 14 tumor cell lines has detectable levels of high affinity cell surface TNF binding sites, thus suggesting that resistance was not often due to the absence of cell surface TNF receptors. Northern blot analysis demonstrated that three of the eleven resistant cell lines expressed detectable levels of TNF mRNA. Furthermore, both sensitive and resistant epithelial tumor cells had the capacity to express TNF transcripts in the presence of the protein synthesis inhibitor, cycloheximide. Finally, the presence of TNF expression at the RNA level is shown to be associated with the production of a TNF-like protein in the resistant Ov-D ovarian carcinoma cells. These findings suggest that certain human epithelial tumor cell lines inherently resistant to TNF also express this cytokine.
Insights
Tumor necrosis factor (TNF) can inhibit tumor growth, but resistance is common. Studies show resistant epithelial tumor cells can still produce TNF, suggesting an intrinsic resistance mechanism.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF) is a cytokine with known anti-tumor properties.
- The mechanisms underlying tumor cell resistance to TNF remain poorly understood.
- Understanding TNF resistance is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the basis of resistance to TNF in human epithelial tumor cell lines.
- To determine if resistant cells express TNF or its receptors.
- To explore the relationship between TNF expression and resistance.
Main Methods:
- Exposure of 14 epithelial tumor cell lines to varying concentrations of TNF.
- Analysis of cell surface TNF binding sites using radioligand binding assays.
- Detection of TNF mRNA levels via Northern blot analysis.
- Assessment of TNF transcript expression in the presence of cycloheximide.
- Characterization of TNF-like protein production in resistant cells.
Main Results:
- Eleven out of 14 epithelial tumor cell lines exhibited resistance to TNF's growth inhibitory effects.
- Most resistant cell lines possessed high-affinity TNF cell surface receptors, indicating resistance is not due to receptor absence.
- Three resistant cell lines expressed detectable TNF mRNA.
- Both sensitive and resistant cells could produce TNF transcripts when protein synthesis was inhibited.
- Resistant ovarian carcinoma cells (Ov-D) produced a TNF-like protein.
Conclusions:
- Human epithelial tumor cell lines resistant to TNF can inherently express this cytokine.
- TNF resistance may involve mechanisms beyond receptor availability, including intrinsic cytokine production.
- Further research is needed to elucidate the precise mechanisms of TNF resistance in cancer.
