Effects of Voluntary Running on Inflammation and Tumor Progression in Mice

Abstract

Objective: Physical activity prevents some cancers and decreases cancer-related deaths. The mechanisms involved remain elusive, due to the difficulties inherent in defining and quantifying physical activity in human subjects, as well as the limitations in obtaining tissue samples for mechanistic studies. The purpose of my research was to establish a mouse model of voluntary wheel running, which could be used to study the effects of physical activity on tumor progression. I studied the role of inflammation as it is associated with cancer, whereas physical activity has been documented to present an anti-inflammatory effect in lab animals and humans. I hypothesized that voluntary running will alter signaling mechanisms associated with inflammatory components of the innate immune system, resulting in an anti-tumor effect.

Results: Two months of voluntary wheel running in PyMT transgenic mice was significantly associated with decreased gene expression of CCL22, a marker for regulatory T-cells, and enhanced gene expression of CXCR4, a marker of tumor invasion and metastasis, but not with other markers of tumor-associated macrophages nor with markers of tumor proliferation. The distances ran by the PyMT mice were also correlated with decreased tumor burden during the first month of running, suggesting a dose-dependent response of tumor growth to increased physical activity.

Wild-type mice given free access to running wheel for 5 days per week, one hour per day for 5 months demonstrated improved lean mass and decreased fat mass, but showed no differences in glucose tolerance with non-runners.

Finally, aged BALB/c mice given wheel access for two months prior to tumor implants demonstrated significant correlations between the distance ran and i) tumor mass and ii) tumor mitotic index, and weak correlations with tumor necrosis.

Conclusions: Regular physical activity has an early effect in attenuating tumor growth and during the later stages of tumor progression, suppresses the recruitment of regulatory T-cells in PyMT transgenic mice. Thus, physical activity may be useful as an adjunct supplement to cancer immunotherapy. Increased physical activity is also significantly correlated with decreased tumor burden in aged mice. Translationally, older women at risk of breast cancer may also benefit from increased physical activity.