Cited by 103Escherichia coli research studiesImmune cells in cancerCancer Research and Treatments

Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression

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Raisch, Jennifer, Rolhion, Nathalie, Dubois, Anaëlle, Darfeuille-Michaud, Arlette, Bringer, Marie-Agnès·2015·Laboratory Investigation

Abstract

Intestinal dysbiosis has been reported in patients with colorectal cancer, and there is a high prevalence of Escherichia coli belonging to B2 phylogroup and producing a genotoxin, termed colibactin. Macrophages are one of the predominant tumor-infiltrating immune cells supporting key processes in tumor progression by producing protumoral factors such as cyclooxygenase-2 (COX-2). Here, we investigated whether B2 E. coli colonizing colon tumors could influence protumoral activities of macrophages. In contrast to commensal or nonpathogenic E. coli strains that were efficiently and rapidly degraded by macrophages at 24 h after infection, colon cancer-associated E. coli were able to resist killing by human THP-1 macrophages, to replicate intracellularly, and to persist inside host cells until at least 72 h after infection. Significant increases in COX-2 expression were observed in macrophages infected with colon cancer E. coli compared with macrophages infected with commensal and nonpathogenic E. coli strains or uninfected cells at 72 h after infection. Induction of COX-2 expression required live bacteria and was not due to colibactin production, as similar COX-2 levels were observed in macrophages infected with the wild-type colon cancer-associated E. coli 11G5 strain or a clbQ mutant unable to produce colibactin. Treatment of macrophages with ofloxacin, an antibiotic with intracellular tropism, efficiently decreased the number of intracellular bacteria and suppressed bacteria-induced COX-2 expression. This study provides new insights into the understanding of how tumor- infiltrating bacteria could influence cancer progression through their interaction with immune cells. Manipulation of microbes associated with tumors could have a deep influence on the secretion of protumoral molecules by infiltrating macrophages.

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Crossref · 10.1038/labinvest.2014.161

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  • In colorectal cancer patients, microbiota composition is one factor favoring carcinogenic lesions, notably through genotoxic bacteria such as Fusobacterium nucleatum or colibactin-producing Escherichia coli.

    “In CRC patients, it is known that the composition of the microbiota is one of the factors favoring the development of carcinogenic lesions, notably by the presence of genotoxic bacteria such as Fusobacterium nucleatum or colibactin-producing Escherichia coli (124, 125).”

    From Bifidobacteria and Their Health-Promoting Effects (2017) · cites this paper as [124]

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Research works printed but not linked: 3

  1. Martin HM, Campbell BJ, Hart CA, et al. Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer. Gastroenterology 2004;127:80-93.
  2. Bamba H, Ota S, Kato A, et al. High expression of cyclooxygenase-2 in macrophages of human colonic adenoma. Int J Cancer 1999; 83:470-475.
  3. Hull MA, Faluyi OO, Ko CW, et al. Regulation of stromal cell cyclo- oxygenase-2 in the ApcMin/ þ mouse model of intestinal tumori- genesis. Carcinogenesis 2006;27:382-391.

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Authors
Raisch, J., Rolhion, N., Dubois, A., Darfeuille-Michaud, A., & Bringer, M.-A.
Affiliations
  • Inserm (FR)
  • Imperial College London (GB)
Corresponding author
Bringer, Marie-Agnès
Venue
Laboratory Investigation
Publisher
Elsevier BV
Published
2015-03
Volume
95
Issue
3
Pages
296-307
ISSN
0023-6837 (ISSN-L)
OpenAlex
W2094274080
Cited by
100
References
62
Citations by year
2026: 4 · 2025: 7 · 2024: 13 · 2023: 6 · 2022: 9 · 2021: 16 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 7 · 2015: 1
FWCI
4.23
Type
journal article
Language
en
Open access
Locations
  • Laboratory Investigation (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Imperial College London
  • Institut National de la Santé et de la Recherche Médicale (UMR 1071, USC-2018)
  • Ligue Contre le Cancer
  • Institut National de la Recherche Agronomique (USC-2018)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
Keywords
colorectal cancer, tumor-associated macrophages, COX-2 expression, intracellular bacterial replication, colibactin, ofloxacin, THP-1 macrophages, gut dysbiosis
MeSH terms
Colonic Neoplasms, Escherichia coli, Humans, Macrophages, Peptides, Vacuoles, Immunoblotting, Dinoprostone, Microscopy, Confocal, Cell Line, Tumor, Microscopy, Electron, Transmission, p38 Mitogen-Activated Protein Kinases, Microbial Viability, Cyclooxygenase 2, Host-Pathogen Interactions, Polyketides

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