Back to Search
Start Over
Predominant T helper type 2-inflammatory responses promote murine colon cancers
- Source :
- International Journal of Cancer. 118:2232-2236
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-gamma) gene deficient (-/-) [Th2 dominant] or interleukin (IL)-4(-/-) [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirty-three weeks after initial treatment, the total colon was examined. When IFN-gamma(-/-) mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 +/- 1.7) than in WT (3.3 +/- 2.9) or IL-4(-/-) (3.1 +/- 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-gamma(-/-) mice than in IL-4(-/-) mice. Histologically, the tumors were well- or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-gamma(-/-) mice showed distinct nuclear expression of beta-catenin, in contrast to the strong membrane staining seen in tumors of IL-4(-/-) mice. In conclusion, colonic inflammation associated with Th2-dominant cytokine responses enhanced the formation of malignant neoplasms.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Colon
medicine.medical_treatment
Adenocarcinoma
medicine.disease_cause
Interferon-gamma
Mice
chemistry.chemical_compound
Th2 Cells
medicine
Animals
Neoplasm Invasiveness
Interferon gamma
Colitis
Interleukin 4
Inflammation
Mice, Knockout
Mice, Inbred BALB C
business.industry
Azoxymethane
Interleukin
medicine.disease
Ulcerative colitis
Cytokine
Oncology
chemistry
Colonic Neoplasms
Cancer research
Colitis, Ulcerative
Interleukin-4
business
Carcinogenesis
medicine.drug
Subjects
Details
- ISSN :
- 10970215 and 00207136
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- International Journal of Cancer
- Accession number :
- edsair.doi.dedup.....a4d1b1db3df291b5e09996b7cdeaeeba