Intracellular and Interstitial Expression of Helicobacter Pylori Virulence Genes in Gastric Precancerous Intestinal Metaplasia and Adenocarcinoma

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2003 Apr 16

PMID 12695995

Citations 64

Authors

Cristina Semino-Mora

Sonia Q Doi

Aileen Marty

Vlado Simko

Ingemar Carlstedt

Andre Dubois

Affiliations

Soon will be listed here.

Abstract

Gastric intestinal metaplasia (IM) and gastric cancer are associated with Helicobacter pylori, but the bacterium often is undetectable in these lesions. To unravel this apparent paradox, IM, H. pylori presence, and the expression of H. pylori virulence genes were quantified concurrently using histologic testing, in situ hybridization, and immunohistochemistry. H. pylori was detected inside metaplastic, dysplastic, and neoplastic epithelial cells, and cagA and babA2 expression was colocalized. Importantly, expression of cagA was significantly higher in patients with IM and adenocarcinoma than in control subjects. The preneoplastic "acidic" MUC2 mucin was detected only in the presence of H. pylori, and MUC2 expression was higher in patients with IM, dysplasia, and cancer. These novel findings are compatible with the hypothesis that all stages of gastric carcinogenesis are fostered by persistent intracellular expression of H. pylori virulence genes, especially cagA inside MUC2-producing precancerous gastric cells and pleomorphic cancer cells.

Citing Articles

The Role of Mucin Expression in the Diagnosis of Oesophago-Gastric Cancer: A Systematic Literature Review.

Patel N, Geropoulos G, Patel P, Bhogal R, Harrington K, Singanayagam A Cancers (Basel). 2023; 15(21).

PMID: 37958425 PMC: 10650431. DOI: 10.3390/cancers15215252.

How Long Will It Take to Launch an Effective Vaccine for Humans?.

Li S, Zhao W, Xia L, Kong L, Yang L Infect Drug Resist. 2023; 16:3787-3805.

PMID: 37342435 PMC: 10278649. DOI: 10.2147/IDR.S412361.

The Efficacy of Cancer Immunotherapies Is Compromised by Infection.

Oster P, Vaillant L, McMillan B, Velin D Front Immunol. 2022; 13:899161.

PMID: 35677057 PMC: 9168074. DOI: 10.3389/fimmu.2022.899161.

An Overview of Autophagy in Infection and Related Gastric Cancer.

Yang Y, Shu X, Xie C Front Cell Infect Microbiol. 2022; 12:847716.

PMID: 35463631 PMC: 9033262. DOI: 10.3389/fcimb.2022.847716.

in gastric cancer: Features of infection and their correlations with long-term results of treatment.

Senchukova M, Tomchuk O, Shurygina E World J Gastroenterol. 2021; 27(37):6290-6305.

PMID: 34712033 PMC: 8515796. DOI: 10.3748/wjg.v27.i37.6290.

References

Dalakas M . Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part I: L-carnitine prevents the myotoxicity of AZT in vitro. Lab Invest. 1994; 71(1):102-12. View

Andersen L, Holck S . Possible evidence of invasiveness of Helicobacter (Campylobacter) pylori. Eur J Clin Microbiol Infect Dis. 1990; 9(2):135-8. DOI: 10.1007/BF01963640. View

Jaju R, Haas O, Neat M, Harbott J, Saha V, Boultwood J . A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG). Blood. 1999; 94(2):773-80. View

Stein M, Rappuoli R, Covacci A . Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A. 2000; 97(3):1263-8. PMC: 15590. DOI: 10.1073/pnas.97.3.1263. View

Endoh Y, Tamura G, Motoyama T, Ajioka Y, Watanabe H . Well-differentiated adenocarcinoma mimicking complete-type intestinal metaplasia in the stomach. Hum Pathol. 1999; 30(7):826-32. DOI: 10.1016/s0046-8177(99)90144-2. View

Reis C, David L, Correa P, Carneiro F, de Bolos C, Garcia E . Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Cancer Res. 1999; 59(5):1003-7. View

Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y . Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001; 134(5):380-6. DOI: 10.7326/0003-4819-134-5-200103060-00010. View

Correa P . Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995; 19 Suppl 1:S37-43. View

Parsonnet J, Friedman G, ORENTREICH N, Vogelman H . Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut. 1997; 40(3):297-301. PMC: 1027076. DOI: 10.1136/gut.40.3.297. View

10.

El-Shoura S . Helicobacter pylori: I. Ultrastructural sequences of adherence, attachment, and penetration into the gastric mucosa. Ultrastruct Pathol. 1995; 19(4):323-33. DOI: 10.3109/01913129509064237. View

11.

Tummuru M, Cover T, Blaser M . Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993; 61(5):1799-809. PMC: 280768. DOI: 10.1128/iai.61.5.1799-1809.1993. View

12.

Lan Z, Dai L, Zhuo X, Feng J, Xu K, Chi C . Gene cloning and sequencing of BmK AS and BmK AS-1, two novel neurotoxins from the scorpion Buthus martensi Karsch. Toxicon. 1999; 37(5):815-23. DOI: 10.1016/s0041-0101(98)00221-9. View

13.

Lee H, Ahn D, Crawley S, Li J, Gum Jr J, Basbaum C . Phorbol 12-myristate 13-acetate up-regulates the transcription of MUC2 intestinal mucin via Ras, ERK, and NF-kappa B. J Biol Chem. 2002; 277(36):32624-31. DOI: 10.1074/jbc.M200353200. View

14.

Kwok T, Backert S, Schwarz H, Berger J, Meyer T . Specific entry of Helicobacter pylori into cultured gastric epithelial cells via a zipper-like mechanism. Infect Immun. 2002; 70(4):2108-20. PMC: 127843. DOI: 10.1128/IAI.70.4.2108-2120.2002. View

15.

Steele-Mortimer O, Brumell J, Knodler L, Meresse S, Lopez A, Finlay B . The invasion-associated type III secretion system of Salmonella enterica serovar Typhimurium is necessary for intracellular proliferation and vacuole biogenesis in epithelial cells. Cell Microbiol. 2002; 4(1):43-54. DOI: 10.1046/j.1462-5822.2002.00170.x. View

16.

Wyle F, Tarnawski A, Schulman D, Dabros W . Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study. J Clin Gastroenterol. 1990; 12 Suppl 1:S92-8. DOI: 10.1097/00004836-199001001-00016. View

17.

Ko G, Kang S, Kim Y, Lee J, Park C, Youn H . Invasiveness of Helicobacter pylori into human gastric mucosa. Helicobacter. 1999; 4(2):77-81. DOI: 10.1046/j.1523-5378.1999.98690.x. View

18.

Dalakas M, Semino-Mora C . Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). Lab Invest. 2001; 81(11):1537-44. DOI: 10.1038/labinvest.3780367. View

19.

Fantry G, Zheng Q, Darwin P, Rosenstein A, James S . Mixed infection with cagA-positive and cagA-negative strains of Helicobacter pylori. Helicobacter. 1996; 1(2):98-106. DOI: 10.1111/j.1523-5378.1996.tb00018.x. View

20.

Ho S, Shekels L, Toribara N, Kim Y, Lyftogt C, Cherwitz D . Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Cancer Res. 1995; 55(12):2681-90. View