Human Colon Cancer-Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice
©2022 The Authors; Published by the American Association for Cancer Research..
Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients.
SIGNIFICANCE: Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis. See related commentary by Jain and Dudeja, p. 1838. This article is highlighted in the In This Issue feature, p. 1825.
| Errataetall: |
CommentIn: Cancer Discov. 2022 Aug 5;12(8):1838-1840. - PMID 35929130 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Cancer discovery - 12(2022), 8 vom: 05. Aug., Seite 1873-1885 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Drewes, Julia L [VerfasserIn] |
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| Links: |
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| Themen: |
Bacterial Toxins |
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| Anmerkungen: |
Date Completed 08.08.2022 Date Revised 10.02.2024 published: Print CommentIn: Cancer Discov. 2022 Aug 5;12(8):1838-1840. - PMID 35929130 Citation Status MEDLINE |
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| doi: |
10.1158/2159-8290.CD-21-1273 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Drewes, Julia L |e verfasserin |4 aut | |
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| 500 | |a CommentIn: Cancer Discov. 2022 Aug 5;12(8):1838-1840. - PMID 35929130 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2022 The Authors; Published by the American Association for Cancer Research. | ||
| 520 | |a Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients | ||
| 520 | |a SIGNIFICANCE: Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis. See related commentary by Jain and Dudeja, p. 1838. This article is highlighted in the In This Issue feature, p. 1825 | ||
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