Genetic ablation of Tnfalpha demonstrates no detectable suppressive effect on inflammation-related mouse colon tumorigenesis.

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.