MyD88-mediated signaling prevents development of adenocarcinomas of the colon via interleukin-18. Mus musculus

Inflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis. Overall design: The Myd88 knockout mice were backcrossed to obtain at least 98% congenicity to B6NCr background. As control groups, wild type mice of identical background were used. Ten biological repeats were performed for the treated wild type and Myd88 samples. Six biological repeats were performed for the untreated wild type and Myd88 samples.