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

Alexandra Yin, Nathaniel R. Campbell, Lee W. Jones, Richard M. White

Preprint posted on March 09, 2018

Another string to the bow: Zebrafish can be used to investigate the effect of exercise endurance on melanoma progression

Selected by Jacky G. Goetz

Selected by Jacky G.Goetz (@GoetzJacky) and Gautier Follain (@Follain_Ga, Ph.D student in Jacky’s group)

This preprint from the group of Richard M. White (MSKCC) provides an elegant and original proof of principle for the use of zebrafish (D. rerio) as a relevant model to study the impact of exercise on cancer progression. They first established a flow chamber system, with tunable parameters, that allows to subject embryos and adults to a reproducible paradigm of endurance exercise. They then grafted a previously established zebrafish melanoma cell line and investigated tumor growth in adults and larvae that were forced to exercise in swimming tunnels for two consecutive weeks. Doing so, they show that exercise significantly decreases cancer progression in larvae, but not in adults.

Bigger picture

This proof of principle reveals a new string to the bow of the zebrafish model, which offers a huge number of advantages for studying cancer progression, and beyond. Growing evidence shows that exercise impact cancer progression in patients. Nevertheless, these questions have only been poorly studied so far, and mostly addressed in few studies using rodent models.

This proof of principle study opens multiple doors for interrogating the effect of exercise during cancer progression. The authors nicely described (in the discussion) the multiple options provided by such an assay. For example, one could test:

– 100 to 1000 of animals, which cannot be done with rodents

– CRISPR-mediated tuning of macro/microenvironmental cues

– screen for small molecules, some of which could have therapeutical implications

– transgenic zebrafish lines with full and competent immune systems.

In conclusion, this study, which combines the great advantages of the zebrafish model with a pioneer set-up for interrogating the benefits of exercise during cancer progression, should inspire many studies to come.

Open questions

A few open questions, that should pave the way for future research, remain:

– Is it possible to maintain better survival during experimentation (exercise)?

– Would short intense exercise phenocopy the results obtained with 2weeks endurance?

– What are the effects of regular & intense exercise and metabolic boosters on cancer development?

– Why do embryos/larvae behave differently than adults?

– Do these observations apply to other cancer types?

– Importantly, would exercise prevent metastasis onset and/or progression?

Combining high-throughput imaging of metastasis formation/growth in conditions of exercise would very likely provide useful information as to how we could prevent metastasis formation in a near future.

Figure: Snapshot from Figure 4 : Representative images of tumor-bearing zebrafish larvae, at one or two weeks of the trials. Green color is showing the GFP signal from the transplanted melanoma cells.

Movie : Here, the authors shared a time-lapse imaging of an acute exercise bout in adult zebrafish. Supplemental Movie 1


Tags: cancer, exercise, metabolism

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