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Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth
Abstract
Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.
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“A few mechanistic studies have demonstrated a potential role of other myokines, including Oncostatin M, irisin, and SPARC in the suppression of breast and colon cancer growth (41, 224-227).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [224]
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Background
Metadata
- Authors
- Hojman, P., Dethlefsen, C., Brandt, C., Hansen, J., Pedersen, L., & Pedersen, B. K.
- Affiliations
- Centre of Inflammation and Metabolism at the Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Cophenhagen; and
- University of Copenhagen (DK)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2011-09
- Volume
- 301
- Issue
- 3
- Pages
- E504-E510
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2137928272
- Cited by
- 259
- References
- 27
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 24 · 2023: 21 · 2022: 29 · 2021: 20 · 2020: 26 · 2019: 16 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 11 · 2014: 8 · 2013: 18 · 2012: 7
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- physical activity, myokines, oncostatin M, breast cancer, MCF-7 cells, apoptosis, caspase activity, tumor cell proliferation
- MeSH terms
- Animals, Cells, Cultured, Humans, Physical Conditioning, Animal, Up-Regulation, Cytokines, Muscle, Skeletal, Cell Line, Tumor, Cell Proliferation, Mice
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