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PMID: 18332421 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 11 ·2008-03-18 ·Pages 4358-63

Giannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI

Abstract

We have characterized the adaptations of Helicobacter pylori to a rarely captured event in the evolution of its impact on host biology-the transition from chronic atrophic gastritis (ChAG) to gastric adenocarcinoma-and defined the impact of these adaptations on an intriguing but poorly characterized interaction between this bacterium and gastric epithelial stem cells. Bacterial isolates were obtained from a single human host colonized with a single dominant strain before and after his progression from ChAG to gastric adenocarcinoma during a 4-year interval. Draft genome assemblies were generated from two isolates, one ChAG-associated, the other cancer-associated. The cancer-associated strain was less fit in a gnotobiotic transgenic mouse model of human ChAG and better able to establish itself within a mouse gastric epithelial progenitor-derived cell line (mGEP) that supports bacterial attachment. GeneChip-based comparisons of the transcriptomes of mGEPs and a control mouse gastric epithelial cell line revealed that, upon infection, the cancer-associated strain regulates expression of GEP-associated signaling and metabolic pathways, and tumor suppressor genes associated with development of gastric cancer in humans, in a manner distinct from the ChAG-associated isolate. The effects on GEP metabolic pathways, some of which were confirmed in gnotobiotic mice, together with observed changes in the bacterial transcriptome are predicted to support aspects of an endosymbiosis between this microbe and gastric stem cells. These results provide insights about how H. pylori may adapt to and influence stem cell biology and how its intracellular residency could contribute to gastric tumorigenesis.

MeSH Terms
Animals Biological Evolution Cell Separation Chronic Disease Disease Progression Endoscopy Gastritis, Atrophic/microbiology,pathology Gene Expression Profiling Genome, Bacterial/genetics Helicobacter pylori/genetics,isolation & purification Humans Mice Molecular Sequence Data Phenotype Stem Cells/metabolism Stomach Neoplasms/microbiology,pathology Transcription, Genetic/genetics
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Giannakis Marios
Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108, USA.
Chen Swaine L
Karam Sherif M
Engstrand Lars
Gordon Jeffrey I
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0800668105
Published
2008-03-18
Epub
2008-00-10
Pages
4358-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2393758
Subset
IM
Grants
NIDDK NIH HHS · R01 DK058529 · United States
NIDDK NIH HHS · DK58529 · United States
NIDDK NIH HHS · U01 DK063483 · United States
NIGMS NIH HHS · T32 GM007200 · United States
NIGMS NIH HHS · GM07200 · United States
NIDDK NIH HHS · P30 DK052574 · United States
NIDDK NIH HHS · DK64540 · United States
NIAID NIH HHS · AI068362 · United States
NIDDK NIH HHS · P50 DK064540 · United States
NIAID NIH HHS · F32 AI068362 · United States
NIDDK NIH HHS · DK52574 · United States
NIDDK NIH HHS · DK63483 · United States
Databases
GENBANK
ABJO00000000, ABJO01000000, ABJP00000000, ABJP01000000
GEO
GSE10261, GSE10262
External Links
PubMed source DOI: 10.1073/pnas.0800668105 PMC Full Text View journal details
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