Impact factors that modulate gastric cancer risk in Helicobacter pylori‐infected rodent models

Abstract

Gastric cancer causes a large social and economic burden to humans. Helicobacter pylori (H pylori) infection is a major risk factor for distal gastric cancer. Detailed elucidation of H pylori pathogenesis is significant for the prevention and treatment of gastric cancer. Animal models of H pylori‐induced gastric cancer have provided an invaluable resource to help elucidate the mechanisms of H pylori‐induced carcinogenesis as well as the interaction between host and the bacterium. Rodent models are commonly used to study H pylori infection because H pylori‐induced pathological processes in the stomachs of rodents are similar to those in the stomachs of humans. The risk of gastric cancer in H pylori‐infected animal models is greatly dependent on host factors, bacterial determinants, environmental factors, and microbiota. However, the related mechanisms and the effects of the interactions among these impact factors on gastric carcinogenesis remain unclear. In this review, we summarize the impact factors mediating gastric cancer risk when establishing H pylori‐infected animal models. Clarifying these factors and their potential interactions will provide insights to construct animal models of gastric cancer and investigate the in‐depth mechanisms of H pylori pathogenesis, which might contribute to the management of H pylori‐associated gastric diseases.

The NF-κB Signaling Pathway, the Microbiota, and Gastrointestinal Tumorigenesis: Recent Advances

“…Multiple mechanisms are involved in the interaction between the host and pathogenic H. pylori. Both bacterial and host genetic factors contribute to H. pylori infection-induced chronic inflammation, metaplasia and gastric tumorigenesis (47). From the perspective of bacteria, the virulence factors of H. pylori have been demonstrated to influence this microorganism's pathogenicity.…”

Inhibition of autophagy aggravates DNA damage response and gastric tumorigenesis via Rad51 ubiquitination in response to H. pylori infection

“…In GES-1 cells, H. pylori infection led to significant increases of DNA DSB levels over the infection duration (Figure 1b). To further evaluate these in vitro findings, Mongolian gerbil, a widely used model for investigating H. pylori-induced gastric tumorigenesis, 26 was challenged with Brucella broth (negative control) or with carcinogenic H. pylori 43503 strain. Immunohistochemistry staining was performed to detect H. pylori colonization (Figure ).…”

Activation of Aquaporin 5 by carcinogenic Helicobacter pylori infection promotes epithelial‐mesenchymal transition via the MEK/ERK pathway

“…Emerging epidemiological and clinical case‐control studies have documented the positive association between H. pylori infection and a significantly higher risk of gastric cancer 5,6 . This relationship has been confirmed in experimental mouse models including C57BL/6 mice, Mongolian gerbils, and transgenic hypergastrinemic mice 7 . CagA, a key virulence factor of H. pylori infection delivered into gastric epithelial cells, is responsible for DNA damage, the inflammatory response, aberrant cell proliferation, and apoptosis through regulation of oncogenic or tumor suppressor genes 8 .…”

“…5,6 This relationship has been confirmed in experimental mouse models including C57BL/6 mice, Mongolian gerbils, and transgenic hypergastrinemic mice. 7 CagA, a key virulence factor of H. pylori infection delivered into gastric epithelial cells, is responsible for DNA damage, the inflammatory response, aberrant cell proliferation, and apoptosis through regulation of oncogenic or tumor suppressor genes. 8 However, the mechanisms by which H. pylori infection induces gastric carcinogenesis remain incompletely elucidated.…”