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Helicobacter pylori infection and stem cells at the origin of gastric cancer

Oncogene volume 34, pages 2547–2555 (2015)Cite this article

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Abstract

Helicobacter pylori infection is now recognized as the main and specific infectious cause of cancer in the world. It is responsible for gastric adenocarcinomas of both intestinal and diffuse types, which are the long-term consequences of the chronic infection of the gastric mucosa. Case–control studies have shown an association between the two, recognized as early as 1994 and further substantiated by interventional studies in which H. pylori eradication has led to the prevention of at least part of the gastric cancers. Experimental studies have highlighted the role of bone marrow-derived cells (BMDCs) and particularly mesenchymal stem cells, in the neoplastic process in about a quarter of the cases and possibly an epithelial–mesenchymal transition (EMT) in the other cases. Different studies have confirmed that chronic infection with H. pylori induces a chronic inflammation and subsequent damage of the gastric epithelial mucosa, leading to BMDC recruitment. Once recruited, these cells home and differentiate by cell–cell fusion with local gastric epithelial cells, bearing local stem cell failure and participating in tissue regeneration. The context of chronic infection and inflammation leads to an EMT and altered tissue regeneration and differentiation from both local epithelial stem cells and BMDC. EMT induces the emergence of CD44+ cells possessing mesenchymal and stem cell properties, resulting in metaplastic and dysplastic lesions to give rise, after additional epigenetic and mutational events, to the emergence of cancer stem cells (CSCs) and adenocarcinoma.

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References

  1. IARC'Working'Group. Schistosomes, Liver Flukes and Helicobacter Pylori: Views and Expert Opinion of IARC Working Group on the Evaluation of Carcinogenic Risks to Humans IARC Monographs. International Agency for research on Cancer: Lyon, France 1994; 61: 177–240.

  2. HaCCG . Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001; 49: 347–353.

    Google Scholar 

  3. Ekstrom AM, Held M, Hansson LE, Engstrand L, Nyren O . Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection. Gastroenterology 2001; 121: 784–791.

    CAS  PubMed  Google Scholar 

  4. Gonzalez CA, Megraud F, Buissonniere A, Lujan Barroso L, Agudo A, Duell EJ et al. Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project. Ann Oncol. 2012; 23: 1320–1324.

    CAS  PubMed  Google Scholar 

  5. Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 2008; 372: 392–397.

    PubMed  Google Scholar 

  6. Lee YC, Chen TH, Chiu HM, Shun CT, Chiang H, Liu TY et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut 2013; 62: 676–682.

    PubMed  Google Scholar 

  7. Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 2004; 291: 187–194.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. de Sablet T, Piazuelo MB, Shaffer CL, Schneider BG, Asim M, Chaturvedi R et al. Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk. Gut 2011; 60: 1189–1195.

    CAS  PubMed  Google Scholar 

  10. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M . Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology 1998; 115: 642–648.

    CAS  PubMed  Google Scholar 

  11. Lee A, O'Rourke J, De Ungria MC, Robertson B, Daskalopoulos G, Dixon MF . A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology 1997; 112: 1386–1397.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  13. Thompson LJ, Danon SJ, Wilson JE, O'Rourke JL, Salama NR, Falkow S et al. Chronic Helicobacter pylori infection with Sydney strain 1 and a newly identified mouse-adapted strain (Sydney strain 2000) in C57BL/6 and BALB/c mice. Infect Immun 2004; 72: 4668–4679.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Hahm KB, Lee KM, Kim YB, Hong WS, Lee WH, Han SU et al. Conditional loss of TGF-beta signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice. Alimentary pharmacology & therapeutics 2002; 16: 115–127.

    CAS  Google Scholar 

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

    PubMed  Google Scholar 

  16. Ohtani M, Garcia A, Rogers AB, Ge Z, Taylor NS, Xu S et al. Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. Carcinogenesis 2007 Dec; 28: 2597–2604.

    CAS  PubMed  Google Scholar 

  17. Takaishi S, Cui G, Frederick DM, Carlson JE, Houghton J, Varro A et al. Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer. Gastroenterology 2005; 128: 1965–1983.

    CAS  PubMed  Google Scholar 

  18. Kuzushita N, Rogers AB, Monti NA, Whary MT, Park MJ, Aswad BI et al. p27kip1 deficiency confers susceptibility to gastric carcinogenesis in Helicobacter pylori-infected mice. Gastroenterology 2005; 129: 1544–1556.

    CAS  PubMed  Google Scholar 

  19. Fox JG, Rogers AB, Whary MT, Ge Z, Ohtani M, Jones EK et al. Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 −/− C57BL6 x Sv129 Helicobacter pylori-infected mice. Am J Pathol 2007; 171: 1520–1528.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Judd LM, Bredin K, Kalantzis A, Jenkins BJ, Ernst M, Giraud AS . STAT3 activation regulates growth, inflammation, and vascularization in a mouse model of gastric tumorigenesis. Gastroenterology 2006; 131: 1073–1085.

    CAS  PubMed  Google Scholar 

  22. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993; 342: 575–577.

    CAS  PubMed  Google Scholar 

  23. Lauren P . The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965; 64: 31–49.

    CAS  PubMed  Google Scholar 

  24. Correa P . Human gastric carcinogenesis: a multistep and multifactorial process—First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992; 52: 6735–6740.

    CAS  PubMed  Google Scholar 

  25. Cahill RJ, Kilgallen C, Beattie S, Hamilton H, O'Morain C . Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma. Gut 1996; 38: 177–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Moss SF, Calam J, Agarwal B, Wang S, Holt PR . Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut 1996; 38: 498–501.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Touati E, Michel V, Thiberge JM, Wuscher N, Huerre M, Labigne A . Chronic Helicobacter pylori infections induce gastric mutations in mice. Gastroenterology 2003; 124: 1408–1419.

    CAS  PubMed  Google Scholar 

  28. Kang GH, Lee HJ, Hwang KS, Lee S, Kim JH, Kim JS . Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation. Am J Pathol 2003; 163: 1551–1556.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Wu CY, Kuo KN, Wu MS, Chen YJ, Wang CB, Lin JT . Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease. Gastroenterology 2009; 137: 1641–1648 e1-2.

    PubMed  Google Scholar 

  30. Suzuki R, Shiota S, Yamaoka Y . Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori. Infect Genet Evol 2012; 12: 203–213.

    PubMed  Google Scholar 

  31. Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ . Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 1997; 112: 92–99.

    CAS  PubMed  Google Scholar 

  32. Ferreira RM, Machado JC, Letley D, Atherton JC, Pardo ML, Gonzalez CA et al. A novel method for genotyping Helicobacter pylori vacA intermediate region directly in gastric biopsy specimens. J Clin Microbiol. 2012; 50: 3983–3989.

    PubMed  PubMed Central  Google Scholar 

  33. Galmiche A, Rassow J, Doye A, Cagnol S, Chambard JC, Contamin S et al. The N-terminal 34 kDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c release. EMBO J 2000; 19: 6361–6370.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Cover TL, Krishna US, Israel DA, Peek RM Jr . Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin. Cancer Res 2003; 63: 951–957.

    CAS  PubMed  Google Scholar 

  35. Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R . Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science (New York, NY) 2003; 301: 1099–1102.

    CAS  Google Scholar 

  36. Ghiara P, Marchetti M, Blaser MJ, Tummuru MK, Cover TL, Segal ED et al. Role of the Helicobacter pylori virulence factors vacuolating cytotoxin, CagA, and urease in a mouse model of disease. Infect Immun 1995; 63: 4154–4160.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Marchetti M, Arico B, Burroni D, Figura N, Rappuoli R, Ghiara P . Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science (New York, NY) 1995; 267: 1655–1658.

    CAS  Google Scholar 

  38. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH et al. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 1995; 55: 2111–2115.

    CAS  PubMed  Google Scholar 

  39. Kuipers EJ, Perez-Perez GI, Meuwissen SG, Blaser MJ . Helicobacter pylori and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst. 1995; 87: 1777–1780.

    CAS  PubMed  Google Scholar 

  40. Occhialini A, Marais A, Urdaci M, Sierra R, Munoz N, Covacci A et al. Composition and gene expression of the cag pathogenicity island in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica. Infect Immun 2001; 69: 1902–1908.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Parsonnet J, Friedman GD, Orentreich N, Vogelman H . Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 1997; 40: 297–301.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Backert S, Selbach M . Role of type IV secretion in Helicobacter pylori pathogenesis. Cell Microbiol. 2008; 10: 1573–1581.

    CAS  PubMed  Google Scholar 

  43. Backert S, Clyne M, Tegtmeyer N . Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Commun Signal 2011; 9: 28.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol. 2004; 5: 1166–1174.

    CAS  PubMed  Google Scholar 

  45. Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science (New York, NY) 2002; 295: 683–686.

    CAS  Google Scholar 

  46. Lu H, Murata-Kamiya N, Saito Y, Hatakeyama M . Role of partitioning-defective 1/microtubule affinity-regulating kinases in the morphogenetic activity of Helicobacter pylori CagA. J Biol Chem 2009; 284: 23024–23036.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Backert S, Tegtmeyer N, Selbach M . The versatility of Helicobacter pylori CagA effector protein functions: The master key hypothesis. Helicobacter 2010; 15: 163–176.

    CAS  PubMed  Google Scholar 

  48. Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA 2008; 105: 1003–1008.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Leblond CP, Stevens CE, Bogoroch R . Histological localization of newly-formed desoxyribonucleic acid. Science 1948; 108: 531–533.

    CAS  PubMed  Google Scholar 

  50. Okumura T, Ericksen RE, Takaishi S, Wang SS, Dubeykovskiy Z, Shibata W et al. K-ras mutation targeted to gastric tissue progenitor cells results in chronic inflammation, an altered microenvironment, and progression to intraepithelial neoplasia. Cancer Res 2010; 70: 8435–8445.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Peterson AJ, Menheniott TR, O'Connor L, Walduck AK, Fox JG, Kawakami K et al. Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans. Gastroenterology 2010; 139: 2005–2017.

    CAS  PubMed  Google Scholar 

  52. Quante M, Marrache F, Goldenring JR, Wang TC . TFF2 mRNA transcript expression marks a gland progenitor cell of the gastric oxyntic mucosa. Gastroenterology 2010; 139: 2018–2027 e2.

    CAS  PubMed  Google Scholar 

  53. Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 2010; 6: 25–36.

    CAS  PubMed  Google Scholar 

  54. Wu C, Xie Y, Gao F, Wang Y, Guo Y, Tian H et al. Lgr5 expression as stem cell marker in human gastric gland and its relatedness with other putative cancer stem cell markers. Gene 2013; 525: 18–25.

    CAS  PubMed  Google Scholar 

  55. Nam KT, Lee HJ, Sousa JF, Weis VG, O'Neal RL, Finke PE et al. Mature chief cells are cryptic progenitors for metaplasia in the stomach. Gastroenterology 2010; 139: 2028–2037 e9.

    CAS  PubMed  Google Scholar 

  56. Qiao XT, Ziel JW, McKimpson W, Madison BB, Todisco A, Merchant JL et al. Prospective identification of a multilineage progenitor in murine stomach epithelium. Gastroenterology 2007; 133: 1989–1998.

    CAS  PubMed  Google Scholar 

  57. Stange DE, Koo BK, Huch M, Sibbel G, Basak O, Lyubimova A et al. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 2013; 155: 357–368.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells (Dayton, OH) 2009; 27: 1006–1020.

    CAS  Google Scholar 

  59. Ponta H, Sherman L, Herrlich PA . CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003; 4: 33–45.

    CAS  PubMed  Google Scholar 

  60. Solis MA, Chen YH, Wong TY, Bittencourt VZ, Lin YC, Huang LL . Hyaluronan regulates cell behavior: a potential niche matrix for stem cells. Biochem Res Int 2012; 2012: 346972.

    PubMed  PubMed Central  Google Scholar 

  61. Su YJ, Lai HM, Chang YW, Chen GY, Lee JL . Direct reprogramming of stem cell properties in colon cancer cells by CD44. EMBO J 2011; 30: 3186–3199.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Khurana SS, Riehl TE, Moore BD, Fassan M, Rugge M, Romero-Gallo J et al. The hyaluronic acid receptor CD44 coordinates normal and metaplastic gastric epithelial progenitor cell proliferation. J Biol Chem 2013; 288: 16085–16097.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H et al. Gastric cancer originating from bone marrow-derived cells. Science (New York, NY) 2004; 306: 1568–1571.

    CAS  Google Scholar 

  64. Varon C, Dubus P, Mazurier F, Asencio C, Chambonnier L, Ferrand J et al. Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice. Gastroenterology 2012; 142: 281–291.

    PubMed  Google Scholar 

  65. Nam KT, Lee HJ, Mok H, Romero-Gallo J, Crowe JE Jr, Peek RM Jr, et al. Amphiregulin-deficient mice develop spasmolytic polypeptide expressing metaplasia and intestinal metaplasia. Gastroenterology 2009; 136: 1288–1296.

    CAS  PubMed  Google Scholar 

  66. Weis VG, Goldenring JR . Current understanding of SPEM and its standing in the preneoplastic process. Gastric Cancer. 2009; 12: 189–197.

    PubMed  Google Scholar 

  67. Ferrand J, Lehours P, Schmid-Alliana A, Megraud F, Varon C . Helicobacter pylori infection of gastrointestinal epithelial cells in vitro induces mesenchymal stem cell migration through an NF-kappaB-dependent pathway. PLoS ONE 2011; 6: e29007.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Ferrand J, Noel D, Lehours P, Prochazkova-Carlotti M, Chambonnier L, Menard A et al. Human bone marrow-derived stem cells acquire epithelial characteristics through fusion with gastrointestinal epithelial cells. PLoS ONE 2011; 6: e19569.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Hutchinson L, Stenstrom B, Chen D, Piperdi B, Levey S, Lyle S et al. Human Barrett's adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant. Stem Cells Dev 2011; 20: 11–17.

    CAS  PubMed  Google Scholar 

  70. Sarosi G, Brown G, Jaiswal K, Feagins LA, Lee E, Crook TW et al. Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett's esophagus. Dis Esophagus 2008; 21: 43–50.

    CAS  PubMed  Google Scholar 

  71. Janin A, Murata H, Leboeuf C, Cayuela JM, Gluckman E, Legres L et al. Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation. Blood 2009; 113: 1834–1840.

    CAS  PubMed  Google Scholar 

  72. Worthley DL, Ruszkiewicz A, Davies R, Moore S, Nivison-Smith I, Bik To L et al. Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation. Stem cells (Dayton, OH) 2009; 27: 1463–1468.

    CAS  Google Scholar 

  73. Almeida R, Almeida J, Shoshkes M, Mendes N, Mesquita P, Silva E et al. OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric carcinomas and binds to, but does not transactivate, CDX2 in gastric cells. J Pathol 2005; 207: 396–401.

    CAS  PubMed  Google Scholar 

  74. Barros R, da Costa LT, Pinto-de-Sousa J, Duluc I, Freund JN, David L et al. CDX2 autoregulation in human intestinal metaplasia of the stomach: impact on the stability of the phenotype. Gut 2011; 60: 290–298.

    CAS  PubMed  Google Scholar 

  75. Zhu Y, Jiang Q, Lou X, Ji X, Wen Z, Wu J et al. MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells. PLoS ONE 2012; 7: e35147.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S . Disruption of the epithelial apical–junctional complex by Helicobacter pylori CagA. Science (New York, NY) 2003; 300: 1430–1434.

    CAS  Google Scholar 

  77. Kalluri R, Weinberg RA . The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119: 1420–1428.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Thiery JP . Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002; 2: 442–454.

    CAS  PubMed  Google Scholar 

  79. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY et al. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704–715.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Segal ED, Cha J, Lo J, Falkow S, Tompkins LS . Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes in Helicobacter pylori. Proc Natl Acad Sci USA 1999; 96: 14559–14564.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Bagnoli F, Buti L, Tompkins L, Covacci A, Amieva MR . Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. Proc Natl Acad Sci USA 2005; 102: 16339–16344.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Yin Y, Grabowska AM, Clarke PA, Whelband E, Robinson K, Argent RH et al. Helicobacter pylori potentiates epithelial:mesenchymal transition in gastric cancer: links to soluble HB-EGF, gastrin and matrix metalloproteinase-7. Gut 2010; 59: 1037–1045.

    CAS  PubMed  Google Scholar 

  83. Baud J, Varon C, Chabas S, Chambonnier L, Darfeuille F, Staedel C . Helicobacter pylori initiates a mesenchymal transition through ZEB1 in gastric epithelial cells. PLoS ONE 2013; 8: e60315.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Bessède E, Staedel C, Acuna Amador LA, Nguyen PH, Chambonnier L, Hatakeyama M et al. Helicobacter pylori generates cells with cancer stem cell properties via epithelial–mesenchymal transition-like changes. Oncogene 2013.

  85. Palena C, Hamilton DH, Fernando RI . Influence of IL-8 on the epithelial–mesenchymal transition and the tumor microenvironment. Fut Oncol (London, England) 2012; 8: 713–722.

    CAS  Google Scholar 

  86. Watanabe T, Takahashi A, Suzuki K, Kurusu-Kanno M, Yamaguchi K, Fujiki H et al. Epithelial–mesenchymal transition in human gastric cancer cell lines induced by TNF-alpha-inducing protein of Helicobacter pylori. Int J Cancer 2014; 134: 2373–2382.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This project was supported by SIRIC BRIO (Site de Recherche Intégrée sur le Cancer – Bordeaux Recherche Intégrée Oncologie) [Grant: INCa-DGOS-Inserm 6046]. We thank Geneviève Belleannée (Service Anatomopathologie, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux France) for her help in histopathological analysis of human gastric adenocarcinoma cases.

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  1. Laboratoire de Bactériologie, University of Bordeaux, Bordeaux, France

    E Bessède, F Mégraud & C Varon

  2. INSERM U853, Bordeaux, France

    E Bessède, F Mégraud & C Varon

  3. Laboratoire d’Histologie, University of Bordeaux, Bordeaux, France

    P Dubus

  4. EA2406 Histologie et pathologie moléculaire des tumeurs, University of Bordeaux, Bordeaux, France

    P Dubus

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Bessède, E., Dubus, P., Mégraud, F. et al. Helicobacter pylori infection and stem cells at the origin of gastric cancer. Oncogene 34, 2547–2555 (2015). https://doi.org/10.1038/onc.2014.187

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