Bacterial Infection Promotes Colon Tumorigenesis inApc^Min/+Mice

Abstract

The Min mouse, which has a germ line mutation in 1 allele of the Apc tumor suppressor gene, is a model for the early steps in human colorectal cancer. Helicobacter pylori infection, a known risk factor for gastric cancer in humans, causes chronic inflammation and increased epithelial cell proliferation in the stomach. Infection with the bacterium Citrobacter rodentium is known to increase epithelial cell proliferation and to promote chemically initiated tumors in the colon of mice. Min mice infected with C. rodentium at 1 month of age were found to have a 4-fold increase in the number of colonic adenomas at 6 months of age, compared with uninfected Min mice. Most of the colonic adenomas in the infected Min mice were in the distal colon, where C. rodentium-induced hyperplasia occurs. These data demonstrate that bacterial infection promotes colon tumor formation in genetically susceptible mice.

Helicobacter Infection Is Required for Inflammation and Colon Cancer in Smad3-Deficient Mice

“…À/À and IL-10 À/À mice (1,3,7,8,34,35). However, because deficiencies in RAG2 or IL-10 are not part of the known genetic alterations or pathways that contribute to colorectal cancer in humans, it is unclear how Helicobacter spp.…”

CD4+CD25+ Regulatory Lymphocytes Induce Regression of Intestinal Tumors in ApcMin/+ Mice

“…Indeed, there was minimal histologic evidence of intestinal inflammation in mice in our study. However, earlier studies have shown that bacterial infections in the intestine, with concomitant mucosal inflammation, facilitate the development of intestinal adenomas in Apc Min /+ mice (22). Regulatory lymphocytes have well-documented abilities to suppress bacterially triggered inflammatory responses in the bowel of mice (23)(24)(25)(26)(27).…”

Sphingosine-1-Phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again

“…74 Numerous genetic, dietary and environmental modifiers of tumorigenicity in Min mice exist, indicating that the ultimate effect of aberrant Wnt signaling involves complex molecular interactions. 75,76 Well-recognized modifiers of human CRC and polyposis in Min mice include high-fat diets and modulators of lipid metabolism and inflammation. 77,78 Further, dietary sphingolipids have been shown to affect b-catenin activation and intestinal tumorigenesis in Min mice.…”