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Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner.

Goh J, Tsai J, Bammler TK, Farin FM, Endicott E, Ladiges WC - PLoS ONE (2013)

Bottom Line: Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence.It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved.These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Program in Nutritional Sciences, University of Washington, Seattle, Washington, United States of America ; Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT) mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p ≤ 0.01), and the greater the running distance the smaller the tumor size (Pearson's r = -0.61, p ≤ 0.04, R(2) = 0.38). Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p ≤ 0.05). Adipose tissue mass was inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014) but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p ≤ 0.005). No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.

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Spleen weights obtained at sacrifice in transgenic (N = 7 runners and 8 non-runners) and wild-type mice (N = 3 per condition) were increased in transgenic non-runners compared with wild-type runners (p = 0.03), but no other significant differences were observed.
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pone-0080123-g004: Spleen weights obtained at sacrifice in transgenic (N = 7 runners and 8 non-runners) and wild-type mice (N = 3 per condition) were increased in transgenic non-runners compared with wild-type runners (p = 0.03), but no other significant differences were observed.

Mentions: Spleeen weight has been used as a surrogate biomarker for immune function and inflammation in transgenic mouse models of breast cancer [4], [5]. In this present study, we observed a significant difference in spleen weights across transgenic runners, non-runners and wild-type runners and non-runners, p = 0.01, F = 4.945 (Figure 4). There were no significant differences in spleen weight (normalized for body weight) at sacrifice between transgenic runners and non-runners, or between wild-type (F1 hybrids not expressing the PyMT transgene) runners and non-runners. Compared between genotypes, transgenic runners demonstrated higher spleen weights than wild-type runners, but this did not reach statistical significance. Spleen weights from transgenic and wild-type non-runners demonstrated the same pattern, while wild type runners had lower spleen weights, compared with transgenic non-runners (p = 0.03).


Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner.

Goh J, Tsai J, Bammler TK, Farin FM, Endicott E, Ladiges WC - PLoS ONE (2013)

Spleen weights obtained at sacrifice in transgenic (N = 7 runners and 8 non-runners) and wild-type mice (N = 3 per condition) were increased in transgenic non-runners compared with wild-type runners (p = 0.03), but no other significant differences were observed.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842299&req=5

pone-0080123-g004: Spleen weights obtained at sacrifice in transgenic (N = 7 runners and 8 non-runners) and wild-type mice (N = 3 per condition) were increased in transgenic non-runners compared with wild-type runners (p = 0.03), but no other significant differences were observed.
Mentions: Spleeen weight has been used as a surrogate biomarker for immune function and inflammation in transgenic mouse models of breast cancer [4], [5]. In this present study, we observed a significant difference in spleen weights across transgenic runners, non-runners and wild-type runners and non-runners, p = 0.01, F = 4.945 (Figure 4). There were no significant differences in spleen weight (normalized for body weight) at sacrifice between transgenic runners and non-runners, or between wild-type (F1 hybrids not expressing the PyMT transgene) runners and non-runners. Compared between genotypes, transgenic runners demonstrated higher spleen weights than wild-type runners, but this did not reach statistical significance. Spleen weights from transgenic and wild-type non-runners demonstrated the same pattern, while wild type runners had lower spleen weights, compared with transgenic non-runners (p = 0.03).

Bottom Line: Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence.It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved.These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Program in Nutritional Sciences, University of Washington, Seattle, Washington, United States of America ; Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT) mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p ≤ 0.01), and the greater the running distance the smaller the tumor size (Pearson's r = -0.61, p ≤ 0.04, R(2) = 0.38). Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p ≤ 0.05). Adipose tissue mass was inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014) but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p ≤ 0.005). No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.

Show MeSH
Related in: MedlinePlus