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Virulence of Helicobacter pylori infection and gastric cancer: lessons from mouse models

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Abstract

Although discovered only recently, Helicobacter pylori is now considered the prototype for bacteria capable of promoting cancer in humans. Shortly after its isolation and identification in 1982, Marshall and Warren quickly recognized that the human pathogen H. pylori might be responsible for both peptic ulcer disease and gastric cancer. The bacterium was strongly associated with chronic active gastritis, long known to precede cancer, and infection with the organism was endemic in those parts of the world where gastric cancer is prevalent. Given the widespread prevalence of H. pylori infection throughout the world, it was understandable that the proposed link between the bacteria and stomach cancer met with some initial scepticism. Nevertheless, evidence in support of this theory has continued to accumulate and the link between H. pylori and gastric cancer has become less debatable. The H. pylori-gastric cancer connection is now supported by multiple lines of evidence, ranging from clinical epidemiological investigations to prospective observational studies to animal models. However, at a basic level many questions remain. Gastric cancer is the eventual outcome in only 1% of infected individuals; why then does gastric cancer develop in some individuals (but not others), and how does chronic H. pylori infection lead to gastric cancer?

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References

  1. Park WS, Oh RR, Park JY et al. Somatic mutations of the trefoil factor family 1 gene in gastric cancer. Gastroenterology. 2000; 119: 691–8.

    Article  PubMed  CAS  Google Scholar 

  2. Li QL, Ito K, Sakakura C et al. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 2002; 109: 113–14.

    Article  PubMed  CAS  Google Scholar 

  3. Houghton JM, Bloch LM, Goldstein M, Von Hagen S, Korah RM. In vivo disruption of the fas pathway abrogates gastric growth alterations secondary to Helicobacter infection. J Infect Dis. 2000; 182: 856–64.

    Article  PubMed  CAS  Google Scholar 

  4. Wang TC, Fox JG. Helicobacter pylori and gastric cancer: Koch’s postulates fulfilled. Gastroenterology. 1998; 115: 780–83.

    Article  PubMed  CAS  Google Scholar 

  5. Fox JG, Wang TC. Helicobacter pylori - not a good bug after all! N Engl J Med. 2001; 345: 829–32.

    Article  PubMed  CAS  Google Scholar 

  6. Fox JG, Wishnok JS, Murphy JC, Tannenbaum SR, Correa P. MNNG-induced gastric carcinoma in ferrets infected with Helicobacter mustelae. Carcinogenesis. 1993; 14: 1957–61.

    Article  PubMed  CAS  Google Scholar 

  7. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterology. 1998; 115: 642–8.

    Article  PubMed  CAS  Google Scholar 

  8. Lee A, Fox JG, Otto G, Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology. 1990; 99: 1315–23.

    PubMed  CAS  Google Scholar 

  9. Fox JG, Sheppard BJ, Dangler CA, Whary MT, Ihrig M, Wang TC. Germ-line p53-targeted disruption inhibits Helicobacter-induced premalignant lesions and invasive gastric carcinoma through downregulation of Thl proinflammatory responses. Cancer Res. 2002; 62: 696–702.

    PubMed  CAS  Google Scholar 

  10. Wang T, Dangler CA, Chen C et al. Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric carcinoma. Gastroenterology. 2000; 118: 36–47.

    Article  PubMed  CAS  Google Scholar 

  11. Wang TC, Goldenring JR, Ito S et al. C57BL/6 mice deficient in secretory phospholipase A2 show increased apoptosis and altered cellular differentiation after Helicobacter felis infection. Gastroenterology. 1998; 114: 675–89.

    Article  PubMed  CAS  Google Scholar 

  12. Schmidt PH, Lee JR, Joshi V et al. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest. 1999; 79: 639–46.

    PubMed  CAS  Google Scholar 

  13. Fox JG, Dangler CA, Whary MT, Edelman W, Kucherlapati R, Wang TC. Mice carrying a truncated Apc gene have diminished gastric epithelial proliferation, gastric inflammation, and humoral immunity in response to Helicobacter felis infection. Cancer Res. 1997; 57: 3972–8.

    PubMed  CAS  Google Scholar 

  14. Xu X, Brodie SG, Yang X et al. Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice. Oncogene. 2000; 19: 1868–74.

    Article  PubMed  CAS  Google Scholar 

  15. Tebbutt NC, Giraud AS, Inglese M et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nature Med. 2002; 8: 1089–97.

    Article  PubMed  CAS  Google Scholar 

  16. Serafini M, Bellocco R, Wolk A, Ekstrom AM. Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology. 2002; 123: 985–91.

    Article  PubMed  CAS  Google Scholar 

  17. Fox JG, Dangler CA, Taylor NS, King A,Koh TH, Wang TC. High salt diet induces gastric epithelial hyperplasia, parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res. 1999; 59: 4823–8.

    PubMed  CAS  Google Scholar 

  18. Dockray GJ, Varro A, Dimaline R, Wang TC. Progastrin-derived peptides and their biological activities. Annu Rev Physiol. 2001; 63: 119–40.

    Article  PubMed  CAS  Google Scholar 

  19. Zavros Y, Rieder G, Ferguson A, Samuelson LC, Merchant JL. Hypergastrinemia in response to gastric inflammation suppresses somatostatin. Am J Physiol Gastrointest Liver Physiol. 2002; 282: G175–83.

    PubMed  CAS  Google Scholar 

  20. Chen D, Zhao C-M, Dockray GJ et al. Glycine-extended gastrin synergizes with gastrin-17 to stimulate acid secretion in gastrin-deficient mice. Gastroenterology. 2000; 119: 756–65.

    Article  PubMed  CAS  Google Scholar 

  21. Fox JG, Beck P, Dangler CA et al. Concurrent enteric helminth infection modulates inflammation, gastric immune responses, and reduces Helicobacter-induced gastric atrophy. Nature Med. 2000; 6: 536–42.

    Article  PubMed  CAS  Google Scholar 

  22. Zavros Y, Rieder G, Ferguson A, Merchant JL. Gastritis and hypergastrinemia due to Acinetobacter lwoffii in mice. Infect Immun. 2002; 70: 2630–9.

    Article  PubMed  CAS  Google Scholar 

  23. Zavros Y, Rieder G, Ferguson A, Samuelson LC, Merchant JL. Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice. Gastroenterology. 2002; 122: 119–33.

    Article  PubMed  Google Scholar 

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Wang, T.C., Fox, J.G., Houghton, JM. (2003). Virulence of Helicobacter pylori infection and gastric cancer: lessons from mouse models. In: Hunt, R.H., Tytgat, G.N.J. (eds) Helicobactor pylori. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1763-2_18

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  • DOI: https://doi.org/10.1007/978-94-017-1763-2_18

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5778-5

  • Online ISBN: 978-94-017-1763-2

  • eBook Packages: Springer Book Archive

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