Obesity promotes colonic stem cell expansion during cancer initiation

V. DeClercq; D. N. McMurray; R. S. Chapkin

doi:10.1016/j.canlet.2015.10.001

Obesity promotes colonic stem cell expansion during cancer initiation

V. DeClercq, D. N. McMurray, R. S. Chapkin

Medicine

Medicine

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39 Citas (Scopus)

Resumen

There is an urgent need to elucidate the mechanistic links between obesity and colon cancer. Convincing evidence for the role of Lgr5⁺ stem cells in colon tumorigenesis has been established; however, the influence of obesity on stem cell maintenance is unknown. We assessed the effects of high fat (HF) feeding on colonic stem cell maintenance during cancer initiation (AOM induced) and the responsiveness of stem cells to adipokine signaling pathways. The number of colonic GFP⁺ stem cells was significantly higher in the AOM-injected HF group compared to the LF group. The Lgr5⁺ stem cells of the HF fed mice exhibited statistically significant increases in cell proliferation and decreases in apoptosis in response to AOM injection compared to the LF group. Colonic organoid cultures from lean mice treated with an adiponectin receptor agonist exhibited a reduction in Lgr5-GPF⁺ stem cell number and an increase in apoptosis; however, this response was diminished in the organoid cultures from obese mice. These results suggest that the responsiveness of colonic stem cells to adiponectin in diet-induced obesity is impaired and may contribute to the stem cell accumulation observed in obesity.

Idioma original	English
Páginas (desde-hasta)	336-343
Número de páginas	8
Publicación	Cancer Letters
Volumen	369
N.º	2
DOI	https://doi.org/10.1016/j.canlet.2015.10.001
Estado	Published - dic. 28 2015

Nota bibliográfica

Funding Information:
The authors would like to thank Dr. Laurie Davidson and Dr. Yang-Yi Fan for technical assistance, and Evelyn Callaway for technical assistance and mouse breeding. V.D., D.N.M., and R.S.C. designed the research; V.D. conducted the research, analyzed data and performed statistical analysis; V.D. and R.S.C. wrote the paper; V.D. and R.S.C. had primary responsibility for final content. All authors have read and approved the final content of the manuscript. Funding from NIH CA129444 , CA168312 , P30ES023512 and the American Institute for Cancer Research supported this work.

Publisher Copyright:
© 2015 Elsevier Ireland Ltd.

ASJC Scopus Subject Areas

Oncology
Cancer Research

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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10.1016/j.canlet.2015.10.001

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title = "Obesity promotes colonic stem cell expansion during cancer initiation",

abstract = "There is an urgent need to elucidate the mechanistic links between obesity and colon cancer. Convincing evidence for the role of Lgr5+ stem cells in colon tumorigenesis has been established; however, the influence of obesity on stem cell maintenance is unknown. We assessed the effects of high fat (HF) feeding on colonic stem cell maintenance during cancer initiation (AOM induced) and the responsiveness of stem cells to adipokine signaling pathways. The number of colonic GFP+ stem cells was significantly higher in the AOM-injected HF group compared to the LF group. The Lgr5+ stem cells of the HF fed mice exhibited statistically significant increases in cell proliferation and decreases in apoptosis in response to AOM injection compared to the LF group. Colonic organoid cultures from lean mice treated with an adiponectin receptor agonist exhibited a reduction in Lgr5-GPF+ stem cell number and an increase in apoptosis; however, this response was diminished in the organoid cultures from obese mice. These results suggest that the responsiveness of colonic stem cells to adiponectin in diet-induced obesity is impaired and may contribute to the stem cell accumulation observed in obesity.",

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note = "Funding Information: The authors would like to thank Dr. Laurie Davidson and Dr. Yang-Yi Fan for technical assistance, and Evelyn Callaway for technical assistance and mouse breeding. V.D., D.N.M., and R.S.C. designed the research; V.D. conducted the research, analyzed data and performed statistical analysis; V.D. and R.S.C. wrote the paper; V.D. and R.S.C. had primary responsibility for final content. All authors have read and approved the final content of the manuscript. Funding from NIH CA129444 , CA168312 , P30ES023512 and the American Institute for Cancer Research supported this work. Publisher Copyright: {\textcopyright} 2015 Elsevier Ireland Ltd.",

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N2 - There is an urgent need to elucidate the mechanistic links between obesity and colon cancer. Convincing evidence for the role of Lgr5+ stem cells in colon tumorigenesis has been established; however, the influence of obesity on stem cell maintenance is unknown. We assessed the effects of high fat (HF) feeding on colonic stem cell maintenance during cancer initiation (AOM induced) and the responsiveness of stem cells to adipokine signaling pathways. The number of colonic GFP+ stem cells was significantly higher in the AOM-injected HF group compared to the LF group. The Lgr5+ stem cells of the HF fed mice exhibited statistically significant increases in cell proliferation and decreases in apoptosis in response to AOM injection compared to the LF group. Colonic organoid cultures from lean mice treated with an adiponectin receptor agonist exhibited a reduction in Lgr5-GPF+ stem cell number and an increase in apoptosis; however, this response was diminished in the organoid cultures from obese mice. These results suggest that the responsiveness of colonic stem cells to adiponectin in diet-induced obesity is impaired and may contribute to the stem cell accumulation observed in obesity.

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Obesity promotes colonic stem cell expansion during cancer initiation

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODS de las Naciones Unidas

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