Helicobacter hepaticus Infection Promotes Colon Tumorigenesis in the BALB/c- Rag2 ^−/− Apc ^{Min /+} Mouse

Abstract

؊/؊ Apc Min/؉ ) was generated. BALB-RagMin mice had a significant increase in tumors in the small, but not large, intestine relative to their BALB-Min counterparts (43.0 versus 24.0 tumors/mouse, respectively). The results suggest that the adaptive immune system plays a role in either the elimination or the equilibrium phase of cancer immunoediting in the small intestine in this model. We investigated the effect of the enterohepatic bacterial pathogen Helicobacter hepaticus on liver and intestine tumorigenesis in BALB-RagMin mice. H. hepaticus-infected BALB-RagMin mice developed moderate hepatitis, moderate typhlitis, and mild colitis. There were no differences in small intestine and cecal tumor multiplicity, regionality, or size relative to that in uninfected mice. However, H. hepaticus-infected BALB-RagMin mice had a significant increase in colon tumor incidence relative to uninfected BALB-RagMin mice (23.5% versus 1.7%, respectively). The data suggest that H. hepaticus, which is present in many research colonies, promotes colon tumorigenesis in the BALB-RagMin mouse and that it has the potential to confound colon tumorigenesis studies.

Long-lived intestinal tuft cells serve as colon cancer–initiating cells

“…These results are in line with previous reports (29) and argue against a prominent role of DCLK1 + cells as quiescent or reserve stem cells. Interestingly, while the number of DCLK1 + cells did not increase with acute injury, we observed an expansion of these cells in the setting of chronic injury, inflammation, and preneoplasia, including that associated with chronic infection with B. fragilis (55) and H. hepaticus (56,57). These find- (60).…”

Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis -induced colon tumorigenesis

“…Taken together, these histopathological and gene expression data indicate that pharmacological inhibition of SMO by MDL 72527 reduces ETBFassociated intestinal chronic inflammation and proliferation. of the immune response to bacteria that may be involved in either promoting or protecting against intestinal inflammation and carcinogenesis (31)(32)(33)(34)(35)(36). The importance of bacterially-induced ROS in inflammation-associated carcinogenesis was demonstrated in mice lacking the H 2 O 2 detoxification enzymes gpx-1 and gpx-2.…”

Remote Control of Intestinal Tumorigenesis by Innate Immunity

“…Conversely, in formerly germ-free animals, the development of azoxymethaneinduced colon tumors resumes after colonization by certain indigenous microorganisms, including Bacteroides vulgatus (3). Furthermore, Helicobacter hepaticus infection has been linked to enhanced tumorigenesis within the descending colon and rectum in animals intrinsically carrying a highly penetrant mutation (referred to as Apc Min/+ ) in the adenomatous polyposis coli (Apc) gene (4). In humans, Apc is a tumor suppressor gene that is highly mutated in both familial and sporadic colon cancer syndromes.…”