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Helicobacter Species pp 157–173Cite as

Mouse Models of Helicobacter-Induced Gastric Cancer: Use of Cocarcinogens

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 921))

Abstract

The human pathogen Helicobacter pylori causes inflammation in the stomach of infected hosts, leading in some cases to the development of gastric cancer. Several mouse models have been developed to study Helicobacter-induced carcinogenesis with similarities to gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma (MALToma) in humans. These models require chronic infection of animals with mouse-colonizing isolates of H. pylori or with related gastric Helicobacter spp., such as the canine/feline species Helicobacter felis. Furthermore, consistent with the known influence of host and environmental factors in human gastric cancer, it is possible to manipulate the type and severity of gastric lesions in mouse Helicobacter infection models through the use of different mouse genetic backgrounds and/or by the administration of known cocarcinogens, such as alkylating agents (e.g., N-nitroso-N-methylurea), or even elevated quantities of dietary salt. Here, we describe protocols for the inoculation of mice with gastric Helicobacter spp. and the administration of these cocarcinogens. Furthermore, we will describe the various methodologies used to study gastric inflammation and carcinogenesis in Helicobacter-infected animals.

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References

  1. Danon SJ, Eaton KA (1998) The role of gastric Helicobacter and N-methyl-N′-nitro- N-nitrosoguanidine in carcinogenesis of mice. Helicobacter 3:260–268

    Article  PubMed  CAS  Google Scholar 

  2. Sakagami T, Dixon M, O’Rourke J, Howlett R, Alderuccio F, Vella J et al (1996) Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis. Gut 39:639–648

    Article  PubMed  CAS  Google Scholar 

  3. Cai X, Carlson J, Stoicov C, Li H, Wang TC, Houghton J (2005) Helicobacter felis eradication restores normal architecture and inhibits gastric cancer progression in C57BL/6 mice. Gastroenterology 128:1937–1952

    Article  PubMed  CAS  Google Scholar 

  4. Enno A, O’Rourke JL, Howlett CR, Jack A, Dixon MF, Lee A (1995) MALToma-like lesions in the murine gastric mucosa after long-term infection with Helicobacter felis A mouse model of Helicobacter pylori-induced gastric lymphoma. Am J Pathol 147:217–222

    PubMed  CAS  Google Scholar 

  5. Ferrero RL, Thiberge JM, Huerre M, Labigne A (1998) Immune responses of specific-pathogen-free mice to chronic Helicobacter pylori (strain SS1) infection. Infect Immun 66:1349–1355

    PubMed  CAS  Google Scholar 

  6. Rogers AB, Taylor NS, Whary MT, Stefanich ED, Wang TC, Fox JG (2005) Helicobacter pylori but not high salt induces gastric intraepithelial neoplasia in B6129 mice. Cancer Res 65:10709–10715

    Article  PubMed  CAS  Google Scholar 

  7. Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B et al (2008) Overexpression of interleukin-1β induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14:408–419

    Article  PubMed  CAS  Google Scholar 

  8. Wang TC, Dangler CA, Chen D, Goldenring JR, Koh T, Raychowdhury R et al (2000) Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology 118:36–47

    Article  PubMed  CAS  Google Scholar 

  9. Han SU, Kim YB, Joo HJ, Hahm KB, Lee WH, Cho YK et al (2002) Helicobacter pylori infection promotes gastric carcinogenesis in a mice model. J Gastroenterol Hepatol 17:253–261

    Article  PubMed  Google Scholar 

  10. Shimizu N, Kaminishi M, Tatematsu M, Tsuji E, Yoshikawa A, Yamaguchi H et al (1998) Helicobacter pylori promotes development of pepsinogen-altered pyloric glands, a preneoplastic lesion of glandular stomach of BALB/c mice pretreated with N-methyl-N-nitrosourea. Cancer Lett 123:63–69

    Article  PubMed  CAS  Google Scholar 

  11. Fox JG, Dangler CA, Taylor NS, King A, Koh TJ, Wang TC (1999) High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res 59:4823–4828

    PubMed  CAS  Google Scholar 

  12. Lee A, O’Rourke J, De Ungria MC, Robertson B, Daskalopoulos G, Dixon MF (1997) A standardized mouse model of Helicobacter pylori infection: Introducing the Sydney strain. Gastroenterology 112:1386–1397

    Article  PubMed  CAS  Google Scholar 

  13. Israel DA, Salama N, Arnold CN, Moss SF, Ando T, Wirth HP et al (2001) Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses. J Clin Invest 107:611–620

    Article  PubMed  CAS  Google Scholar 

  14. Fox JG, Batchelder M, Marini R, Yan L, Handt L, Li X et al (1995) Helicobacter pylori-induced gastritis in the domestic cat. Infect Immun 63:2674–2681

    PubMed  CAS  Google Scholar 

  15. Lee A, Hazell SL, O’Rourke J, Kouprach S (1988) Isolation of a spiral-shaped bacterium from the cat stomach. Infect Immun 56:2843–2850

    PubMed  CAS  Google Scholar 

  16. Ferrero RL, Thiberge JM, Kansau I, Wuscher N, Huerre M, Labigne A (1995) The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice. Proc Natl Acad Sci U S A 92:6499–6503

    Article  PubMed  CAS  Google Scholar 

  17. Corthesy-Theulaz I, Porta N, Glauser M, Saraga E, Vaney AC, Haas R et al (1995) Oral immunization with Helicobacter pylori urease B subunit as a treatment against Helicobacter infection in mice. Gastroenterology 109:115–121

    Article  PubMed  CAS  Google Scholar 

  18. Fox JG, Li X, Cahill RJ, Andrutis K, Rustgi AK, Odze R et al (1996) Hypertrophic ­gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizygous transgenic mice. Gastroenterology 110:155–166

    Article  PubMed  CAS  Google Scholar 

  19. Fox JG, Rogers AB, Ihrig M, Taylor NS, Whary MT, Dockray G et al (2003) Helicobacter pylori-associated gastric cancer in INS-GAS mice is gender specific. Cancer Res 63:942–950

    PubMed  CAS  Google Scholar 

  20. Fox JG, Wang TC, Rogers AB, Poutahidis T, Ge Z, Taylor N et al (2003) Host and microbial constituents influence Helicobacter pylori-induced cancer in a murine model of hypergastrinemia. Gastroenterology 124:1879–1890

    Article  PubMed  Google Scholar 

  21. De Bock M, Decostere A, Van den Bulck K, Baele M, Duchateau L, Haesebrouck F et al (2005) The inflammatory response in the mouse stomach to Helicobacter bizzozeronii, Helicobacter salomonis and two Helicobacter felis strains. J Comp Pathol 133:83–91

    Article  PubMed  Google Scholar 

  22. Kim JS, Chang JH, Chung SI, Yum JS (2001) Importance of the host genetic background on immune responses to Helicobacter pylori infection and therapeutic vaccine efficacy. FEMS Immunol Med Microbiol 31:41–46

    Article  PubMed  CAS  Google Scholar 

  23. Lemke LB, Ge Z, Whary MT, Feng Y, Rogers AB, Muthupalani S et al (2009) Concurrent Helicobacter bilis infection in C57BL/6 mice attenuates proinflammatory H. pylori-induced gastric pathology. Infect Immun 77:2147–2158

    Article  PubMed  CAS  Google Scholar 

  24. Sutton P (2007) Considering increased mouse stomach mass when calculating prophylactic vaccine ef fi cacy against Helicobacter pylori. Helicobacter 12:210–212

    Article  PubMed  Google Scholar 

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Acknowledgments

RF and PS acknowledge grant support (APP1006010 and APP1002947) from the National Health and Medical Research Council (NHMRC), Australia. The work performed at MIMR is supported by the Victorian Government’s Operational Infrastructure Support Program. RF and PS are NHMRC Senior Research Fellows.

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Authors and Affiliations

  1. Monash Institute of Medical Research, Monash University, Melbourne, VIC, Australia

    Richard L. Ferrero

  2. School of Biotechnology and Biomolecular Sciences, The University of NSW, Kensington, NSW, Australia

    John E. Wilson

  3. Centre for Animal Biotechnology, School of Veterinary Science, The University of Melbourne, Melbourne, VIC, Australia

    Philip Sutton

Authors
  1. Richard L. Ferrero
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  2. John E. Wilson
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  3. Philip Sutton
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Corresponding author

Correspondence to Richard L. Ferrero .

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Editors and Affiliations

  1. Medical School, Dept. Medicine, University of Massachusetts, Plantation Street 364, Worcester, 01635, Massachusetts, USA

    JeanMarie Houghton

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Ferrero, R.L., Wilson, J.E., Sutton, P. (2012). Mouse Models of Helicobacter-Induced Gastric Cancer: Use of Cocarcinogens. In: Houghton, J. (eds) Helicobacter Species. Methods in Molecular Biology, vol 921. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-005-2_20

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  • DOI: https://doi.org/10.1007/978-1-62703-005-2_20

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-004-5

  • Online ISBN: 978-1-62703-005-2

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