Inflammatory responses induced by Helicobacter pylori on the carcinogenesis of gastric epithelial GES‑1 cells

  • Authors:
    • Jianjun Wang
    • Yongliang Yao
    • Qinghui Zhang
    • Shasha Li
    • Lijun Tang
  • View Affiliations

  • Published online on: April 9, 2019     https://doi.org/10.3892/ijo.2019.4775
  • Pages: 2200-2210
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Abstract

Helicobacter pylori (HP) is a pathogenic bacterium associated with chronic gastritis, gastric ulcer and gastric cancer. In the present study, the primary carcinogenesis process of normal gastric epithelial cells (GES‑1) infected with HP was investigated. It was determined that infected gastric mucosal epithelial GES‑1 cells secreted increased interleukin‑8 (IL‑8) and IL‑23, and exhibited enhanced expression of inducible nitric oxide synthase and cyclooxygenase‑2, inducing inflammatory reactions and resulting in apoptosis. The bacterial infection significantly increased the expression of carcinogenesis‑associated genes, including p16, c‑Myc, p53 and p21, as well as the expression of cell surface signaling molecules cluster of differentiation 44 (CD44) and CD54 in GES‑1 cells or tissues of patients with gastritis and gastric cancer in vitro or in vivo. Simultaneously, the migration and invasion abilities of normal gastric epithelial GES‑1 cells were increased following HP infection. These observations demonstrated that the inflammatory response of HP infection could cause normal gastric epithelial cells to undergo significant cancerous reactions, indicating that HP is a risk factor for gastric cancer.

References

1 

Blaser MJ and Berg DE: Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest. 107:767–773. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Safavi M, Sabourian R and Foroumadi A: Treatment of Helicobacter pylori infection: Current and future insights. World J Clin Cases. 4:5–19. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Robinson K, Argent RH and Atherton JC: The inflammatory and immune response to Helicobacter pyloriinfection. Best Pract Res Clin Gastroenterol. 21:237–259. 2007. View Article : Google Scholar

4 

Conteduca V, Sansonno D, Lauletta G, Russi S, Ingravallo G and Dammacco F: H. pylori infection and gastric cancer: State of the art (review). Int J Oncol. 42:5–18. 2013. View Article : Google Scholar

5 

International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risk to Humans, Vol 61: Schistosomotes, Liver Flukes and Helicobacter pylori. IARC; Lyon: 1994

6 

Watanabe T, Tada M, Nagai H, Sasaki S and Nakao M: Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology. 115:642–648. 1998. View Article : Google Scholar : PubMed/NCBI

7 

Honda S, Fujioka T, Tokieda M, Satoh R, Nishizono A and Nasu M: Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res. 58:4255–4259. 1998.PubMed/NCBI

8 

Franco AT, Israel DA, Washington MK, Krishna U, Fox JG, Rogers AB, Neish AS, Collier-Hyams L, Perez-Perez GI, Hatakeyama M, et al: Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc Natl Acad Sci USA. 102:10646–10651. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Montano V, Didelot X, Foll M, Linz B, Reinhardt R, Suerbaum S, Moodley Y and Jensen JD: Worldwide population structure, long-term demography, and local adaptation of Helicobacter pylori. Genetics. 200:947–963. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Miszczyk E, Rudnicka K, Moran AP, Fol M, Kowalewicz-Kulbat M, Druszczyńska M, Matusiak A, Walencka M, Rudnicka W and Chmiela M: Interaction of Helicobacter pylori with C-type lectin dendritic cell-specific ICAM grabbing nonintegrin. J Biomed Biotechnol. 2012:2064632012. View Article : Google Scholar : PubMed/NCBI

11 

Pacifico L, Osborn JF, Tromba V, Romaggioli S, Bascetta S and Chiesa C: Helicobacter pylori infection and extragastric disorders in children: A critical update. World J Gastroenterol. 20:1379–1401. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Chmiela M, Gajewski A and Rudnicka K: Helicobacter pylori vs coronary heart disease - searching for connections. World J Cardiol. 7:187–203. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Buzás GM: Metabolic consequences of Helicobacter pylori infection and eradication. World J Gastroenterol. 20:5226–5234. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Hu Y, He C, Liu JP, Li NS, Peng C, Yang-Ou YB, Yang XY, Lu NH and Zhu Y: Analysis of key genes and signaling pathways involved in Helicobacter pylori-associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data. Helicobacter. 23:e125302018. View Article : Google Scholar : PubMed/NCBI

15 

Chen S, Duan G, Zhang R and Fan Q: Helicobacter pylori cytotoxin-associated gene A protein upregulates α-enolase expression via Src/MEK/ERK pathway: Implication for progression of gastric cancer. Int J Oncol. 45:764–770. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Khatoon J, Prasad KN, Prakash Rai R, Ghoshal UC and Krishnani N: Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer. Br J Biomed Sci. 74:121–126. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

18 

Lin SL, Yeh JL, Tsai PC, Chang TH, Huang WC, Lee ST, Wassler M, Geng YJ and Sulistyowati E: Inhibition of neointima hyperplasia, inflammation, and reactive oxygen species in balloon-injured arteries by HVJ envelope vector-mediated delivery of superoxide dismutase gene. Transl Stroke Res. Sep 6–2018, (Epub ahead of print) http://doi.org/10.1007/s12975-018-0660-9urisimpledoi.org/10.1007/s12975-018-0660-9. View Article : Google Scholar

19 

Jia Q, Feng M, Wang Y and Xue S: Gastric cancer cells in collagen gel matrix: Three-dimensional growth and differential expression of adhesion molecules (CD44s, CD54, E-cadherin). J Biomed Mater Res A. 84:917–925. 2008. View Article : Google Scholar

20 

Tafreshi M, Guan J, Gorrell RJ, Chew N, Xin Y, Deswaerte V, Rohde M, Daly RJ, Peek RM Jr, Jenkins BJ, et al: Helicobacter pylori type IV secretion system and its adhesin subunit, CagL, mediate potent inflammatory responses in primary human endothelial cells. Front Cell Infect Microbiol. 8:222018. View Article : Google Scholar :

21 

Sierra JC, Asim M, Verriere TG, Piazuelo MB, Suarez G, Romero-Gallo J, Delgado AG, Wroblewski LE, Barry DP, Peek RM Jr, et al: Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis. Gut. 67:1247–1260. 2018. View Article : Google Scholar

22 

Müller A and Solnick JV: Inflammation, immunity, and vaccine development for Helicobacter pylori. Helicobacter. 16(Suppl 1): 26–32. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Nguyen TT, Kim SJ, Park JM, Hahm KB and Lee HJ: Repressed TGF-β signaling through CagA-Smad3 interaction as pathogenic mechanisms of Helicobacter pylori-associated gastritis. J Clin Biochem Nutr. 57:113–120. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Blaser MJ and Atherton JC: Helicobacter pylori persistence: Biology and disease. J Clin Invest. 113:321–333. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Wang J, Wu J, Cheng Y, Jiang Y and Li G: Over-expression of microRNA-223 inhibited the proinflammatory responses in Helicobacter pylori-infection macrophages by down-regulating IRAK-1. Am J Transl Res. 8:615–622. 2016.PubMed/NCBI

26 

Panpetch W, Spinler JK, Versalovic J and Tumwasorn S: Characterization of Lactobacillus salivarius strains B37 and B60 capable of inhibiting IL-8 production in Helicobacter pylori-stimulated gastric epithelial cells. BMC Microbiol. 16:2422016. View Article : Google Scholar : PubMed/NCBI

27 

Chongruksut W, Limpakan Yamada S, Chakrabandhu B, Ruengorn C and Nanta S: Correlation of Helicobacter pylori and interleukin-8 mRNA expression in high risk gastric cancer population prediction. World J Gastrointest Oncol. 8:215–221. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Koussoulas V, Vassiliou S, Giamarellos-Bourboulis EJ, Tassias G, Kotsaki A, Barbatzas C and Tzivras M: Implications for a role of interleukin-23 in the pathogenesis of chronic gastritis and of peptic ulcer disease. Clin Exp Immunol. 156:97–101. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, et al: Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA. 105:1003–1008. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Park HS, Wijerathne CUB, Jeong HY, Seo CS, Ha H and Kwun HJ: Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury. J Ethnopharmacol. 216:239–250. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Akeel M, Shehata A, Elhafey A, Elmakki E, Aboshouk T, Ageely H and Mahfouz M: Helicobacter pylorivacA, cagA and iceA genotypes in dyspeptic patients from southwestern region, Saudi Arabia: distribution and association with clinical outcomes and histopathological changes. BMC Gastroenterol. 19:162019. View Article : Google Scholar

32 

Lee KS, Kalantzis A, Jackson CB, O’Connor L, Murata-Kamiya N, Hatakeyama M, Judd LM, Giraud AS and Menheniott TR: Helicobacter pylori CagA Triggers expression of the bactericidal lectin REG3c via gastric STAT3 activation. PLoS One. 7:e307862012. View Article : Google Scholar

33 

Palframan SL, Kwok T and Gabriel K: Vacuolating cytotoxin A (VacA), a key toxin for Helicobacter pylori pathogenesis. Front Cell Infect Microbiol. 2:922012. View Article : Google Scholar : PubMed/NCBI

34 

Raju D, Hussey S, Ang M, Terebiznik MR, Sibony M, Galindo-Mata E, Gupta V, Blanke SR, Delgado A, Romero-Gallo J, et al: Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans. Gastroenterology. 142:1160–1171. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Rassow J and Meinecke M: Helicobacter pylori VacA: A new perspective on an invasive chloride channel. Microbes Infect. 14:1026–1033. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Hisatsune J, Yamasaki E, Nakayama M, Shirasaka D, Kurazono H, Katagata Y, Inoue H, Han J, Sap J, Yahiro K, et al: Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells. Infect Immun. 75:4472–4481. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Amieva MR and El-Omar EM: Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology. 134:306–323. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Wang P, Mei J, Zhang N, Tao J, Tian H and Fu GH: Helicobacter pylori upregulates the expression of p16(INK4) in gastric cancer cells. Hepatogastroenterology. 58:846–853. 2011.PubMed/NCBI

39 

Zhang GX, Gu YH, Zhao ZQ, Xu SF, Zhang HJ, Wang HD and Hao B: Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases. World J Gastroenterol. 10:1759–1762. 2004. View Article : Google Scholar : PubMed/NCBI

40 

Saf C, Gulcan EM, Ozkan F, Cobanoglu Saf SP and Vitrinel A: Assessment of p21, p53 expression, and Ki-67 proliferative activities in the gastric mucosa of children with Helicobacter pylori gastritis. Eur J Gastroenterol Hepatol. 27:155–161. 2015. View Article : Google Scholar

41 

Petersson F, Franzén LE and Borch K: Characterization of the gastric cardia in volunteers from the general population Type of mucosa, Helicobacter pylori infection, inflammation, mucosal proliferative activity, p53 and p21 expression, and relations to gastritis. Dig Dis Sci. 55:46–53. 2010. View Article : Google Scholar

42 

Wei J, Nagy TA, Vilgelm A, Zaika E, Ogden SR, Romero-Gallo J, Piazuelo MB, Correa P, Washington MK, El-Rifai W, et al: Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology. 139:1333–1343. 2010. View Article : Google Scholar : PubMed/NCBI

43 

Xu H, Chaturvedi R, Cheng Y, Bussiere FI, Asim M, Yao MD, Potosky D, Meltzer SJ, Rhee JG, Kim SS, et al: Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: Implications for gastric carcinogenesis. Cancer Res. 64:8521–8525. 2004. View Article : Google Scholar : PubMed/NCBI

44 

Gamboa-Dominguez A, Ubbelohde T, Saqui-Salces M, Romano-Mazzoti L, Cervantes M, Domínguez-Fonseca C, de la Luz Estreber M and Ruíz-Palacios GM: Salt and stress synergize H. pylori-induced gastric lesions, cell proliferation, and p21 expression in Mongolian gerbils. Dig Dis Sci. 52:1517–1526. 2007. View Article : Google Scholar : PubMed/NCBI

45 

Kurosawa A, Miwa H, Hirose M, Tsune I, Nagahara A and Sato N: Inhibition of cell proliferation and induction of apoptosis by Helicobacter pylori through increased phosphorylated p53, p21 and Bax expression in endothelial cells. J Med Microbiol. 51:385–391. 2002. View Article : Google Scholar : PubMed/NCBI

46 

Suzuki M, Mimuro H, Kiga K, Fukumatsu M, Ishijima N, Morikawa H, Nagai S, Koyasu S, Gilman RH, Kersulyte D, et al: Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe. 5:23–34. 2009. View Article : Google Scholar : PubMed/NCBI

47 

Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, Aburatani H, Akiyama T, Peek RM Jr, Azuma T, et al: Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 26:4617–4626. 2007. View Article : Google Scholar : PubMed/NCBI

48 

Gagnaire A, Nadel B, Raoult D, Neefjes J and Gorvel JP: Collateral damage: Insights into bacterial mechanisms that predispose host cells to cancer. Nat Rev Microbiol. 15:109–128. 2017. View Article : Google Scholar : PubMed/NCBI

49 

Chauhan N, Tay ACY, Marshall BJ and Jain U: Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: An overview. Helicobacter. 24:e125442019. View Article : Google Scholar

50 

Kumar S and Dhiman M: Inflammasome activation and regulation during Helicobacter pylori pathogenesis. Microb Pathog. 125:468–474. 2018. View Article : Google Scholar : PubMed/NCBI

51 

Lundgren A, Trollmo C, Edebo A, Svennerholm AM and Lundin BS: Helicobacter pylori-specific CD4+ T cells home to and accumulate in the human Helicobacter pylori-infected gastric mucosa. Infect Immun. 73:5612–5619. 2005. View Article : Google Scholar : PubMed/NCBI

52 

Garay J, Piazuelo MB, Majumdar S, Li L, Trillo-Tinoco J, Del Valle L, Schneider BG, Delgado AG, Wilson KT, Correa P, et al: The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice. Cancer Lett. 371:90–98. 2016. View Article : Google Scholar :

53 

Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H, Shiratori Y and Omata M: Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells. J Biol Chem. 276:44856–44864. 2001. View Article : Google Scholar : PubMed/NCBI

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APA
Wang, J., Yao, Y., Zhang, Q., Li, S., & Tang, L. (2019). Inflammatory responses induced by Helicobacter pylori on the carcinogenesis of gastric epithelial GES‑1 cells. International Journal of Oncology, 54, 2200-2210. https://doi.org/10.3892/ijo.2019.4775
MLA
Wang, J., Yao, Y., Zhang, Q., Li, S., Tang, L."Inflammatory responses induced by Helicobacter pylori on the carcinogenesis of gastric epithelial GES‑1 cells". International Journal of Oncology 54.6 (2019): 2200-2210.
Chicago
Wang, J., Yao, Y., Zhang, Q., Li, S., Tang, L."Inflammatory responses induced by Helicobacter pylori on the carcinogenesis of gastric epithelial GES‑1 cells". International Journal of Oncology 54, no. 6 (2019): 2200-2210. https://doi.org/10.3892/ijo.2019.4775