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Zebrafish as a model to investigate the effects of exercise in cancer

Alexandra Yin, Nathaniel R. Campbell, Lee W. Jones, Richard M. White
doi: https://doi.org/10.1101/279232
Alexandra Yin
1University of Texas McGovern Medical School
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Nathaniel R. Campbell
2Weill-Cornell/Rockefeller/Sloan Kettering Tri-Institutional M.D., Ph.D. Program
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Lee W. Jones
3Department of Medicine, Memorial Sloan Kettering Cancer Center
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Richard M. White
3Department of Medicine, Memorial Sloan Kettering Cancer Center
4Weill-Cornell Medical College
5Department of Cancer Biology & Genetics, Memorial Sloan Kettering Cancer Center
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Abstract

Emerging data indicates that exercise may regulate cancer pathogenesis, but the mechanisms underpinning how it regulates the tumor as well as surrounding microenvironment are poorly understood. Dissecting this complex, highly integrated physiology requires model systems which accurately recapitulate key aspects of human response to exercise, yet permit rapid and unbiased genetic interrogation of relevant pathways. The zebrafish has emerged as a new model for cancer due to its high resolution in vivo imaging and capacity for large-scale, unbiased screening approaches. Here, we have developed a set of tools to study the effects of exercise in a zebrafish model of melanoma. Using a flow chamber, we studied the effects of endurance exercise bouts (3-6 hour/d, 5d/wk for 1 to 3 wks) in both larval and adult zebrafish. The regimen was well tolerated, with no unexpected toxicities or changes in survival. When the zebrafish were transplanted with ZMEL1-GFP melanoma cells, we found that endurance exercise over a 2-week period led to a significant decrease in cancer growth in the larval zebrafish. As zebrafish cancer models show strong conservation in human disease, our findings have direct application to understanding the human exercise/cancer relationship.

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Posted March 09, 2018.
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Zebrafish as a model to investigate the effects of exercise in cancer
Alexandra Yin, Nathaniel R. Campbell, Lee W. Jones, Richard M. White
bioRxiv 279232; doi: https://doi.org/10.1101/279232
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Zebrafish as a model to investigate the effects of exercise in cancer
Alexandra Yin, Nathaniel R. Campbell, Lee W. Jones, Richard M. White
bioRxiv 279232; doi: https://doi.org/10.1101/279232

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