CD44 Plays a Functional Role in -induced Epithelial Cell Proliferation

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Chronic gastric inflammation, typically caused by Helicobacter pylori (H. pylori), is the most consistent lesion leading to cancer. During a well-choreographed interaction between H. pylori and the host, the progression from chronic inflammation to cancer involves gastric epithelial changes with evidence of hyperproliferation. Our knowledge of H. pylori pathogenesis is predominantly based on data generated from gastric cancer cell lines or animal models of inflammation. We report the development and use of a novel model of primary human and mouse cultured gastric epithelial cells that are organized into three-dimensional spheroid units containing a lumen, known as gastric organoids. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human -⁠ and mouse-derived gastric organoids were infected with the bacteria. Cluster-of-differentiation gene (CD44) is a transmembrane receptor responsible for epithelial cell proliferation. We show that CD44 plays a functional role in H. pylori-induced proliferation. In a Mongolian gerbil animal model of H. pylori-induced gastric cancer, we show that inhibiting CD44 blocks epithelial proliferation and subsequently cancer progression in response to bacterial infection. Thus our study provides new insights into the role of CD44 in H. pylori-induced hyperproliferation and progression of gastric disease.

Vyšlo v časopise: CD44 Plays a Functional Role in -induced Epithelial Cell Proliferation. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004663
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004663

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Zdroje

1. Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1 : 1311–1315. 6145023

2. Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M (1975) A model for gastric cancer epidemiology. Lancet 2 : 58–60. 49653

3. Kuipers EJ, Meuwissen SG (1996) Helicobacter pylori and gastric carcinogenesis. Scand J Gastroenterol 218 : 103–105. 8865459

4. Kuipers EJ, Perez-Perez GI, Meuwissen SGM, Blaser MJ (1995) Helicobacter pylori and atrophic gastritis: Importance of the cagA status. J Natl Cancer Inst 87 : 1777–1780. 7473834

5. Kusters JG, van Vliet AH, Kuipers EJ (2006) Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19 : 449–490. 16847081

6. Odenbreit S, Puls J, Sedlmaier B, Gerland E, Fischer W, et al. (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287 : 1497–1500. 10688800

7. Segal ED, Falkow S, Tompkins LS (1996) Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc Natl Acad Sci USA 93 : 1259–1264. 8577751

8. Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, et al. (2002) SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295 : 683–686. 11743164

9. Selbach (2004) The Helicobacter pylori CagA protein induces tyrosine dephosphorylation of ezrin.

10. Oliveira MJ, Costa AM, Costa AC, Ferreira RM, Sampaio P, et al. (2009) CagA associates with c-Met, E-cadherin, and p120-catenin in a multiproteic complex that suppresses Helicobacter pylori-induced cell-invasive phenotype. J Infect Dis 200 : 745–755. doi: 10.1086/604727 19604117

11. Churin Y, Al-Ghoul L, Kepp O, Meyer TF, Birchmeier W, et al. (2003) Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol 161 : 249–255. 12719469

12. Oliveira MJ, Costa AC, Costa AM, Henriques L, Suriano G, et al. (2006) Helicobacter pylori induces gastric epithelial cell invasion in a c-Met and type IV secretion system-dependent manner. J Biol Chem 281 : 34888–34896. 16990273

13. Franco AT, Israel DA, Washington MK, Krishna U, Fox JG, et al. (2005) Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc Natl Acad Sci U S A 102 : 10646–10651. 16027366

14. Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, et al. (2003) Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 300 : 1430–1434. 12775840

15. Saadat I HH, Obuse C, Umeda M, Murata-Kamiya N, Saito Y, Lu H, Ohnishi N, Azuma T, Suzuki A, Ohno S, Hatakeyama M. (2007) Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature 447 : 330–333. 17507984

16. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61 : 1303–1313. 1694723

17. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, et al. (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27 : 1006–1020. doi: 10.1002/stem.30 19415765

18. da Cunha CB, Oliveira C, Wen X, Gomes B, Sousa S, et al. (2010) De novo expression of CD44 variants in sporadic and hereditary gastric cancer. Lab Invest 90 : 1604–1614. doi: 10.1038/labinvest.2010.155 20856229

19. Suzuki M, Mimuro H, Kiga K, Fukumatsu M, Ishijima N, et al. (2009) Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe 5 : 23–34. doi: 10.1016/j.chom.2008.11.010 19154985

20. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H (2002) CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 16 : 3074–3086. 12464636

21. Orian-Rousseau V, Morrison H, Matzke A, Kastilan T, Pace G, et al. (2007) Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin. Mol Biol Cell 18 : 76–83. 17065554

22. Feng R, Aihara E, Kenny S, Yang L, Li J, et al. (2014) Indian Hedgehog Mediates Gastrin-Induced Proliferation in Stomach of Adult Mice. Gastroenterology 147 : 655–666. doi: 10.1053/j.gastro.2014.05.006 24859162

23. Stange DE, Koo BK, Huch M, Sibbel G, Basak O, et al. (2013) Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155 : 357–368. doi: 10.1016/j.cell.2013.09.008 24120136

24. Wroblewski LE, Piazuelo MB, Chaturvedi R, Schumacher M, Aihara E, et al. (2014) Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. Gut In Press.

25. Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, et al. (2014) In Vitro Expansion of Human Gastric Epithelial Stem Cells and Their Responses to Bacterial Infection. Gastroenterology In Press.

26. Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, et al. (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141 : 1762–1772. doi: 10.1053/j.gastro.2011.07.050 21889923

27. Barker N, Huch M, Kujala P, van de Wetering M, Snippert H, et al. (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6 : 25–36. doi: 10.1016/j.stem.2009.11.013 20085740

28. Schumacher MA, Aihara E, Feng R, Engevik AC, Shroyer NF, et al. The use of murine-derived fundic organoids in studies of gastric physiology. Journal of Physiology Provisionally accepted.

29. Schumacher MA, Feng R, Aihara E, Engevik AC, Montrose MH, et al. (2014) Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFkB pathway activation: The use of a novel in vitro model to study epithelial response to infection. Helicobacter In Press.

30. Sause WE, Castillo AR, Ottemann KM (2012) The Helicobacter pylori autotransporter ImaA (HP0289) modulates the immune response and contributes to host colonization. Infect Immun 80 : 2286–2296. doi: 10.1128/IAI.00312-12 22566509

31. Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, et al. (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A 90 : 5791–5795. 8516329

32. Guillemin K, Salama NR, Tompkins LS, Falkow S (2002) Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc Natl Acad Sci U S A 99 : 15136–15141. 12411577

33. Baltrus DA, Amieva MR, Covacci A, Lowe TM, Merrell DS, et al. (2009) The complete genome sequence of Helicobacter pylori strain G27. J Bacteriol 191 : 447–448. doi: 10.1128/JB.01416-08 18952803

34. Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, et al. (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I -⁠ specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93 : 14648–14653. 8962108

35. Romero-Gallo J, Harris EJ, Krishna U, Washington MK, Perez-Perez GI, et al. (2008) Effect of Helicobacter pylori eradication on gastric carcinogenesis. Lab Invest 88 : 328–336. doi: 10.1038/labinvest.3700719 18180700

36. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M (1998) Helicobacter pylori infection induces gastric cancer in mongolian gerbils [In Process Citation]. Gastroenterology 115 : 642–648. 9721161

37. Franco AT, Johnston E, Krishna U, Yamaoka Y, Israel DA, et al. (2008) Regulation of gastric carcinogenesis by Helicobacter pylori virulence factors. Cancer Res 68 : 379–387. doi: 10.1158/0008-5472.CAN-07-0824 18199531

38. Yamaguchi A, Goi T, Yu J, Hirono Y, Ishida M, et al. (2002) Expression of CD44v6 in advanced gastric cancer and its relationship to hematogenous metastasis and long-term prognosis. J Surg Oncol 79 : 230–235. 11920780

39. Khurana SS, Riehl TE, Moore BD, Fassan M, Rugge M, et al. (2013) The hyaluronic acid receptor CD44 coordinates normal and metaplastic gastric epithelial progenitor cell proliferation. J Biol Chem 288 : 16085–16097. doi: 10.1074/jbc.M112.445551 23589310

40. Rodrigues GA, Park M (1994) Autophosphorylation modulates the kinase activity and oncogenic potential of the Met receptor tyrosine kinase. Oncogene 9 : 2019–2027. 8208547

41. Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, et al. (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77 : 261–271. 7513258

42. Maulik G, Madhiwala P, Brooks S, Ma PC, Kijima T, et al. (2002) Activated c-Met signals through PI3K with dramatic effects on cytoskeletal functions in small cell lung cancer. J Cell Mol Med 6 : 539–553. 12611639

43. Jung C, Matzke A, Niemann HH, Schwerk C, Tenenbaum T, et al. (2009) Involvement of CD44v6 in InlB-dependent Listeria invasion. Mol Microbiol 72 : 1196–1207. doi: 10.1111/j.1365-2958.2009.06716.x 19432801

44. Wirth HP, Beins MH, Yang M, Tham KT, Blaser MJ (1998) Experimental infection of Mongolian gerbils with wild-type and mutant Helicobacter pylori strains. Infect Immun 66 : 4856–4866. 9746590

45. Amieva MR, Salama NR, Tompkins LS, Falkow S (2002) Helicobacter pylori enter and survive within multivesicular vacuoles of epithelial cells. Cell Microbiol 4 : 677–690. 12366404

46. Schumacher MA, Donnelly JM, Engevik AC, Xiao C, Yang L, et al. (2012) Gastric Sonic Hedgehog acts as a macrophage chemoattractant during the immune response to Helicobacter pylori. Gastroenterology 142 : 1150–1159. doi: 10.1053/j.gastro.2012.01.029 22285806

47. Lee A, O'Rourke J, Ungria MCd, Robertson B, Daskalopoulos G, et al. (1997) A standardized mouse model of Helicobacter pylori infection: Introducing the Sydney Strain. Gastroenterology 112 : 1386–1397. 9098027

48. Campo GM, Avenoso A, D'Ascola A, Nastasi G, Micali A, et al. (2013) Combined treatment with hyaluronan inhibitor Pep-1 and a selective adenosine A2 receptor agonist reduces inflammation in experimental arthritis. Innate Immu 19 : 462–478. doi: 10.1177/1753425912470391 23283732

49. Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 20 : 1161–1181. 8827022

50. Mahé MM, Aihara E, Schumacher MA, Zavros Y, Montrose MH, et al. (2013) Establishment of gastrointestinal epithelial organoids. Curr Protoc Mouse Biol 3 : 217–240. 25105065