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.
Highlights
There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention
We injected immunocompetent FVB mice orthotopically with syngeneic p53/PTEN double-null (−/−) primary breast cancer cells into the third mammary fat pad located within the axillary region, and applied daily stretching for four weeks
Tumor growth from weeks 2–4 was significantly slower in the stretched mice (repeated measured ANOVA group X time interaction p < 0.001, and tumor volume at euthanasia was 52% smaller in the stretch, compared with the no-stretch group (p < 0.001; Fig. 1B,C)
Summary
There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention. 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. Stretching of tissues is a component of these techniques that has not been extensively studied, but could have important effects on the neoplastic process itself[6] This is supported by a growing body of research pointing to the importance of mechanical factors in the pathophysiology of many diseases, including cancer[21,22]. Our recent studies show that gentle daily stretching for 10 minutes can have profound effects on reducing local connective tissue inflammation and fibrosis in several rodent models via direct mechanical effects on the stretched tissues[23,24,25,26]. We hypothesized that stretching would reduce the growth of tumors implanted within locally stretched tissues and tested this hypothesis in a mouse model of breast cancer
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