Stretching Reduces Tumor Growth in a Mouse Breast Cancer Model

Abstract

There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention. Recent studies have shown that gentle daily stretching for 10 minutes can reduce local connective tissue inflammation and fibrosis. Because mechanical factors within the stroma can influence the tumor microenvironment, we hypothesized that stretching would reduce the growth of tumors implanted within locally stretched tissues and tested this hypothesis in a mouse orthotopic breast cancer model. Female FVB mice (N = 66) underwent bilateral injection of p53/PTEN double-null primary mouse mammary tumor cells into the third mammary fat pad. Mice were randomized to stretch vs. no stretch, and treated for 10 minutes once a day, for four weeks. Tumor volume at end-point was 52% smaller in the stretch group, compared to the no-stretch group (p < 0.001) in the absence of any other treatment. Cytotoxic immune responses were activated and levels of Specialized Pro-Resolving Mediators were elevated in the stretch group. These results suggest a link between immune exhaustion, inflammation resolution and tumor growth. Stretching is a gentle, non-pharmacological intervention that could become an important component of cancer treatment and prevention.

Biomechanical Regulation of Breast Cancer Metastasis and Progression

“…From these studies, one could infer the timeline of the effects of load last around one week. A recent study found that mice that performed stretching exercises after orthotopic implantation of breast cancer cells also had reduced tumor growth (36). These findings are consistent with our results and support that breast cancer growth can be reduced by mechanical stretch.…”

Exercise increases skin graft resistance to rejection

“…Previous reports describing the effects of exercise on various aspects of immunity have been somewhat inconsistent. We observed increased production of IFNγ in the graft‐reactive T cells of transplanted exercised over transplanted control mice, consistent with previous reports describing enhanced IFNγ expression in murine models of physical activity . Research using a similar murine exercise model noted enhanced mobilization and infiltration of NK cells into tumors among exercised mice as a result of catecholamine‐induced IL‐6 production, and some NK cells can be inhibitory in transplantation, but increased NK cell infiltration did not occur in the allografts.…”

“…Recent work demonstrated that voluntary running in tumor‐bearing mice resulted in an ≈60% reduction in tumor growth and dramatically reduced frequency of metastases, due to increased epinephrine‐ and IL‐6‐mediated NK cell mobilization and tumor infiltration in exercising mice . Regular stretching in mice also significantly reduced tumor volume, alongside modestly increased levels of inflammatory cytokines, including IL‐6 and interferon (IFN)γ . These works and others suggest that exercise augments immunity .…”

Mechanical Stretch Kills Transformed Cancer Cells

“…Further, recent findings reveal that the stretching of mice for ten minutes a day for four weeks suppresses the breast cancer growth by 50% compared to the non-stretched controls (Berrueta et al, 2018). From these and other studies, there are strong indications that transformed cancer cells may be mechanically vulnerable and thus sensitive to mechanical forces.…”

“…Studies showing inhibition of tumor growth after stretching or exercise in mice model could be explained through a mechanical force-dependent growth inhibition (Berrueta et al, 2018;Betof et al, 2015). Fluid shear-induced killing of circulating tumor cells and adhesive cancer cells can also be explained by increased sensitivity to mechanical forces (Lien et al, 2013;Regmi et al, 2017).…”