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Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses

  • Preclinical Study
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Abstract

Purpose

Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses, in breast cancer survivors could regulate breast cancer cell viability in vitro.

Methods

Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro.

Results

Six months of training increased VO2peak (16.4 %, p < 0.001) and muscle strength, and reduced resting levels of plasma cholesterol (−18.2 %, p = 0.003) and cytokines. Yet, these systemic adaptations had no effect on breast cancer cell viability in vitro. During 2 h of acute exercise, increases in serum lactate (6-fold, p < 0.001), epinephrine (2.9-fold, p = 0.009), norepinephrine (2.2-fold, p < 0.001), and cytokines, including IL-6 (2.1-fold, p < 0.001) were detected. Incubation with serum obtained after exercise reduced viability by −9.2 % in MCF-7 (p = 0.04) and −9.4 % in MDA-MB-231 (p < 0.001) compared to resting serum.

Conclusion

Systemic changes to a 2 h exercise session reduced breast cancer viability, while adaptations to 6 months of training had no impact. Our data question the prevailing dogma that training-dependent baseline reductions in risk factors mediate the protective effect of exercise on breast cancer. Instead, we propose that the cancer protection is driven by accumulative effects of repeated acute exercise responses.

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Acknowledgments

This work was supported by grants from the Danish Cancer Society, the Danish Cancer Research Foundation, and Dagmar Marshall Fund. The Centre for Physical Activity Research (CFAS) is supported by a grant from TrygFonden. During the study period, the Centre of Inflammation and Metabolism (CIM) was supported by a grant from the Danish National Research Foundation (DNRF55). CIM/CFAS is a member of DD2—The Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research, Grant No. 09-067009 and 09-075724). Ruth Rousing and Hanne Villumsen are acknowledged for their technical assistance.

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Authors and Affiliations

  1. The Centre of Inflammation and Metabolism (CIM) and Centre for Physical Activity Research (CFAS), Rigshospitalet, Faculty of Health Science, Copenhagen University Hospital, 7641, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Christine Dethlefsen, Bente Klarlund Pedersen, Jesper Frank Christensen & Pernille Hojman

  2. The University Hospitals Centre for Health Research, Rigshospitalet, Copenhagen, Denmark

    Christian Lillelund, Julie Midtgaard & Christina Andersen

  3. Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Julie Midtgaard

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  1. Christine Dethlefsen
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  2. Christian Lillelund
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  3. Julie Midtgaard
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  4. Christina Andersen
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  5. Bente Klarlund Pedersen
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  6. Jesper Frank Christensen
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  7. Pernille Hojman
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Correspondence to Pernille Hojman.

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Dethlefsen, C., Lillelund, C., Midtgaard, J. et al. Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses. Breast Cancer Res Treat 159, 469–479 (2016). https://doi.org/10.1007/s10549-016-3970-1

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  • DOI: https://doi.org/10.1007/s10549-016-3970-1

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