RT Journal Article
SR Electronic
T1 Zebrafish as a model to investigate the effects of exercise in cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 279232
DO 10.1101/279232
A1 Alexandra Yin
A1 Nathaniel R. Campbell
A1 Lee W. Jones
A1 Richard M. White
YR 2018
UL http://biorxiv.org/content/early/2018/03/09/279232.abstract
AB 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.