Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-alpha and histamine whereas normal keratinocytes undergo cytolysis.

Abstract

BACKGROUND:

Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-alpha are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-alpha and histamine on cervical carcinoma cell lines was studied.

METHODS AND RESULTS:

TNF-alpha alone induced slight growth inhibition and cell cycle arrest at G0/G1 phase in SiHa cells, but increased their migration. Histamine alone had no effect on cells. In addition, TNF-alpha and histamine in combination showed no additional effect over that by TNF-alpha alone, although SiHa cells were even pretreated with a protein synthesis inhibitor. Furthermore, TNF-alpha-sensitive ME-180 carcinoma cells were also resistant to the combination effect of TNF-alpha and histamine. In comparison, TNF-alpha or histamine alone induced growth inhibition in a non-cytolytic manner in normal keratinocytes, an effect that was further enhanced to cell cytolysis when both mediators acted in combination. Keratinocytes displayed strong TNF receptor (TNFR) I and II immunoreactivity, whereas SiHa and ME-180 cells did not. Furthermore, cervix carcinoma specimens revealed TNF-alpha immunoreactivity in peritumoral cells and carcinoma cells. However, the immunoreactivity of both TNFRs was less intense in carcinoma cells than that in epithelial cells in cervical specimens with non-specific inflammatory changes.

CONCLUSION:

SiHa and ME-180 cells are resistant to the cytolytic effect of TNF-alpha and histamine whereas normal keratinocytes undergo cytolysis, possibly due to the smaller amount of TNFRs in SiHa and ME-180 cells. In the cervix carcinoma, the malignant cells may resist this endogenous cytolytic action and TNF-alpha could even enhance carcinoma cell migration.

• Authors: Nicolae-Costin Diaconu, Jaana Rummukainen, Mikko Mättö, Anita Naukkarinen, Rauno J Harvima, Jukka Pelkonen, Ilkka T Harvima
• Journal: BMC cancer (BMC Cancer) Vol. 8 Pg. 46 (Feb 07 2008) ISSN: 1471-2407 [Electronic] England
• PMID: 18257926 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytotoxins
• DNA, Neoplasm
• Tumor Necrosis Factor-alpha
• Histamine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy)
• Cell Death (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cytotoxins (administration & dosage)
• DNA, Neoplasm (drug effects)
• Drug Evaluation, Preclinical
• Drug Resistance, Neoplasm
• Drug Synergism
• Female
• Histamine (administration & dosage, pharmacology)
• Humans
• Keratinocytes (drug effects, physiology)
• Male
• Middle Aged
• Tumor Necrosis Factor-alpha (administration & dosage, pharmacology)
• Uterine Cervical Neoplasms (drug therapy)