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Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer
BACKGROUND: While self-reported exercise is associated with a reduction in the risk of recurrence in colorectal cancer, the molecular mechanisms underpinning this relationship are unknown. Furthermore, the effect of exercise on intratumoral metabolic processes has not been investigated in detail in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237036/ https://www.ncbi.nlm.nih.gov/pubmed/30473788 http://dx.doi.org/10.1186/s40170-018-0190-7 |
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author | Lu, Min Sanderson, Sydney M Zessin, Amelia Ashcraft, Kathleen A Jones, Lee W Dewhirst, Mark W Locasale, Jason W Hsu, David S |
author_facet | Lu, Min Sanderson, Sydney M Zessin, Amelia Ashcraft, Kathleen A Jones, Lee W Dewhirst, Mark W Locasale, Jason W Hsu, David S |
author_sort | Lu, Min |
collection | PubMed |
description | BACKGROUND: While self-reported exercise is associated with a reduction in the risk of recurrence in colorectal cancer, the molecular mechanisms underpinning this relationship are unknown. Furthermore, the effect of exercise on intratumoral metabolic processes has not been investigated in detail in human cancers. In our current study, we generated six colorectal patient patient-derived xenografts (CRC PDXs) models and treated each PDX to voluntary wheel running (exercise) for 6–8 weeks or no exposure to the wheel (control). A comprehensive metabolomics analysis was then performed on the PDXs to identify exercise induced changes in the tumor that were associated with slower growth. RESULTS: Tumor growth inhibition was observed in the voluntary wheel running group compared to the control group in three of the six models. A metabolomics analysis first revealed that central carbon metabolism was affected in each model irrespective of treatment. Interestingly, comparison of responsive and resistant models showed that levels of metabolites in nucleotide metabolism, known to be coupled to mitochondrial metabolism, were predictive of response. Furthermore, phosphocreatine levels which are linked to mitochondrial energy demands were associated with inhibition of tumor growth. CONCLUSION: Altogether, this study provides evidence that changes to tumor cell mitochondrial metabolism may underlie in part the benefits of exercise. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40170-018-0190-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6237036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62370362018-11-23 Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer Lu, Min Sanderson, Sydney M Zessin, Amelia Ashcraft, Kathleen A Jones, Lee W Dewhirst, Mark W Locasale, Jason W Hsu, David S Cancer Metab Research BACKGROUND: While self-reported exercise is associated with a reduction in the risk of recurrence in colorectal cancer, the molecular mechanisms underpinning this relationship are unknown. Furthermore, the effect of exercise on intratumoral metabolic processes has not been investigated in detail in human cancers. In our current study, we generated six colorectal patient patient-derived xenografts (CRC PDXs) models and treated each PDX to voluntary wheel running (exercise) for 6–8 weeks or no exposure to the wheel (control). A comprehensive metabolomics analysis was then performed on the PDXs to identify exercise induced changes in the tumor that were associated with slower growth. RESULTS: Tumor growth inhibition was observed in the voluntary wheel running group compared to the control group in three of the six models. A metabolomics analysis first revealed that central carbon metabolism was affected in each model irrespective of treatment. Interestingly, comparison of responsive and resistant models showed that levels of metabolites in nucleotide metabolism, known to be coupled to mitochondrial metabolism, were predictive of response. Furthermore, phosphocreatine levels which are linked to mitochondrial energy demands were associated with inhibition of tumor growth. CONCLUSION: Altogether, this study provides evidence that changes to tumor cell mitochondrial metabolism may underlie in part the benefits of exercise. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40170-018-0190-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-15 /pmc/articles/PMC6237036/ /pubmed/30473788 http://dx.doi.org/10.1186/s40170-018-0190-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Lu, Min Sanderson, Sydney M Zessin, Amelia Ashcraft, Kathleen A Jones, Lee W Dewhirst, Mark W Locasale, Jason W Hsu, David S Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
title | Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
title_full | Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
title_fullStr | Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
title_full_unstemmed | Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
title_short | Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
title_sort | exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237036/ https://www.ncbi.nlm.nih.gov/pubmed/30473788 http://dx.doi.org/10.1186/s40170-018-0190-7 |
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