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Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression
Open accessAbstract
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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“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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Background
Metadata
- 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
- hybrid
- doi.org
- Licence
- 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 › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- 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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