Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer Journal Article


Authors: Lu, M.; Sanderson, S. M.; Zessin, A.; Ashcraft, K. A.; Jones, L. W.; Dewhirst, M. W.; Locasale, J. W.; Hsu, D. S.
Article Title: Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer
Abstract: BackgroundWhile 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 6-8weeks 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 thatwere associated with slower growth.ResultsTumor 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.ConclusionAltogether, this study provides evidence that changes to tumor cell mitochondrial metabolism may underlie in part the benefits of exercise.
Keywords: colorectal cancer; metabolism; exercise; diagnosis; respiration; metformin; breast-cancer; expression; lung-cancer; cells; physical-activity; mitochondrial metabolism; hallmarks; patient-derived xenograft; central carbon; supporting aspartate biosynthesis
Journal Title: Cancer & Metabolism
Volume: 6
ISSN: 2049-3002
Publisher: BioMed Central Ltd.  
Date Published: 2018-11-15
Start Page: 14
Language: English
ACCESSION: WOS:000450523600001
DOI: 10.1186/s40170-018-0190-7
PROVIDER: wos
PMCID: PMC6237036
PUBMED: 30473788
Notes: Article -- Source: Wos
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  1. Lee Winston Jones
    177 Jones