A novel mouse model of voluntary stretching and its application in breast cancer research

Background: Stretching exercises such as yoga are recommended for cancer survivors to manage symptoms and promote wellbeing in clinical settings. Although other types of exercise (e.g. running) can reduce the growth of tumors in animal models, the role of stretching on tumor growth remains unclear, and the lack of a preclinical self-stretching model has impeded mechanistic studies on health benefits of stretching. We sought to develop a voluntary stretching animal model to address this research gap and apply it to breast cancer research. Methods: Using food, water, and enrichment in the home cage as motivators for stretching, a two-week 24/7 behavior monitoring was conducted in a video-based customizable home-cage behavior tracking system, Noldus PhenoTyper, to promote self-stretching in FVB mice. Subsequently, this model was utilized in a comparative study of voluntary stretching and voluntary running on tumor growth and plasma protein profiles in the MET-1 orthotopic mammary tumor FVB mouse model. Results: The new voluntary stretching model effectively elicited mouse self-stretching in the custom cage setting in the long-term observation and significantly inhibited tumor growth as effectively as voluntary wheel running. Moreover, plasma proteomic analysis demonstrated that voluntary stretch versus voluntary running distinctly impacted systemic protein profiles, possibly linking to different cellular and molecular mechanisms underlying anti-cancer effects and, potentially, exercise-induced benefits in other health conditions. Conclusion: Our work provides the first preclinical voluntary stretching model, which may be well suited to breast cancer research and a valuable research tool to facilitate investigations of stretching health benefits across various research fields.