title: Genetic ablation of Tnfalpha demonstrates no detectable suppressive effect on inflammation-related mouse colon tumorigenesis.
abstract: Colorectal cancer (CRC) is one of the most serious complications of inflammatory bowel disease. Tumor necrosis factor-alpha (Tnfalpha) is a major mediator of inflammation and there is increasing evidence that Tnfalpha/Tnf-receptor-1 (Tnfr1) signaling may act as an endogenous tumor promoter for colon carcinogenesis. In fact, a previous study revealed that mice lacking Tnfr1 develop significantly fewer colonic tumors in the inflammation-related CRC model. In addition, antibodies against Tnfalpha have been shown to inhibit the development of inflammation-related CRC. In the present study, Apc Min/+; Tnfalpha -/- mice were treated with 2% dextran sodium sulfate (DSS) and the tumor development was compared with Apc Min/+; Tnfalpha +/+ control mice in order to investigate the role of Tnfalpha by itself in the inflammation-related CRC. Surprisingly, there were no detectable differences in either the severity of colonic inflammation or the expression of DSS-induced chemokines and cytokines (Ccl2, Cxcl1, Tnfbeta, Il1beta, Il6, and Cox-2) that relate to the colonic inflammation and tumorigenesis between these two groups. Furthermore, the genetic ablation of Tnfalpha did not suppress the colon tumorigenesis in comparison to the wild-type mice. Our observations suggest that intricate inflammatory responses promote the inflammation-related mouse colon tumorigenesis.
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D003092:Colitis / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics*
chemical_list: D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D053583:Interleukin-1beta; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2