A Novel Preclinical Mouse Model of Voluntary Active Stretching Suppresses Mammary Tumor Progression.

Abstract

Purpose: Although exercise is recommended after a breast cancer diagnosis, most survivors remain physically inactive due to cancer-related physical limitations. Identifying a gentle yet effective exercise modality is a critical but underexplored need in cancer care. This preclinical study aims to address this gap by developing a mouse model of voluntary active stretching to investigate the direct effects of gentle active stretching on mammary tumor growth and metastasis.

Methods: Female FVB mice were used with a video-based customizable home-cage behavior tracking system for behavior modeling. Height-elevated food, water, and enrichment within the home cage were used to promote self-stretching in mice. Subsequently, this model was used to compare the effects of voluntary active stretching and voluntary running on tumor growth and lung metastasis in the MET-1 and 6DT1 orthotopic mammary tumor FVB mouse models. Proteomics analysis of tumor tissue was performed for mechanistic investigation.

Results: The custom cage setting effectively elicited mouse voluntarily active stretching in long-term observation. Both voluntary active stretching and voluntary running significantly suppressed tumor growth in the MET-1 orthotopic mammary tumor model, despite voluntary active stretching being a lower-intensity exercise modality. In a more metastatic 6DT1 orthotopic model, voluntary active stretching reduced primary tumor growth and the incidence of larger lung metastases, whereas voluntary running produced no effect. Proteomics analyses further suggested that voluntary active stretching may induce more favorable molecular changes in primary tumors than voluntary running.

Conclusions: This study establishes a novel preclinical voluntary active stretching model and uncovers an underrecognized therapeutic potential of self-stretching to mitigate mouse mammary cancer progression. These findings provide preclinical evidence that voluntary active stretching has beneficial effects on tumor growth and metastasis in mice and warrants further mechanistic and clinical investigation. This study can serve as a translational bridge for developing gentle human stretching and yoga-based interventions for patients with breast cancer.