Cited by 259Exercise and Physiological ResponsesMuscle Physiology and DisordersCytokine Signaling Pathways and Interactions

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Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth

Hojman, Pernille, Dethlefsen, Christine, Brandt, Claus, Hansen, Jakob, Pedersen, Line, Pedersen, Bente Klarlund·2011·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00520.2010

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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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Background
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Liu, Z., Ke, S., & Wan, Y. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03784-0 · Cited by 9
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Papadopoulos, E., Alibhai, S. M. H., TOMLINSON, G. A., Matthew, A., Nesbitt, M. E., Finelli, A., Trachtenberg, J., & Mina, D. S. (2019) · Cancer Causes & Control · doi:10.1007/s10552-019-01211-0 · Cited by 9
Exercise-Induced Circulating microRNAs: Potential Key Factors in the Control of Breast Cancer
Telles, G. D., Conceição, M. S., VECHIN, F. C., Libardi, C. A., Mori, M. A., Derchain, S., & Ugrinowitsch, C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.800094 · Cited by 8
Role of Oncostatin M in Exercise-Induced Breast Cancer Prevention
Negrini, K. A., Lin, D. W., Shah, D., Wu, H., Wehrung, K. M., Thompson, H. J., Whitcomb, T. L., & Sturgeon, K. M. (2024) · Cancers · doi:10.3390/cancers16152716 · Cited by 8
“We may have been underpowered at n = 7 for a smaller effect size from treadmill running at 0% incline [33].”
BackgroundMethodResultInfluential
Exercise Interventions in Breast Cancer: Molecular Mechanisms, Physical Benefits, and Practical Recommendations
Michou, V., Zervoudis, S., Eskitzis, P., Tsamos, G., Vasdeki, D., Vouxinou, A., Markja, A., & Iatrakis, G. M. (2025) · Medicina · doi:10.3390/medicina61071167 · Cited by 11
“Some studies show that exercise-conditioned serum from animals or BC survivors reduces tumor cell viability in vitro [108,109].”
Striated muscle: an inadequate soil for cancers
Saunders, A. A. E., Thomson, R. E., Goodman, C. A., Anderson, R. L., & Gregorevic, P. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10199-2 · Cited by 8
“Hojman and colleagues demonstrated that serum from mice that underwent exercise, or media from electrically stimulated myotubes, inhibited MCF-7 breast cancer cell proliferation [92].”
Background
Natural killer cells from endurance-trained older adults show improved functional and metabolic responses to adrenergic blockade and mTOR inhibition
Minuzzi, L. G., Batatinha, H., Weyh, C., Lakshmi, V. S. B., Fiuza‐Luces, C., Gálvez, B. G., Lucía, A., Teixeira, A. M., Sommer, N., Neto, J. C. R., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-06057-y · Cited by 10
A combination of myokines and genistein suppresses cancer stemness in MCF-7 human breast cancer cells
Kwon, H., Kim, Y., & Kim, J. (2024) · Nutrition Research and Practice · doi:10.4162/nrp.2024.18.3.436 · Cited by 8
“Myokines, which are cytokines from muscles, play a role in cancer development and the regulation of the immune system [11,12].”
Background
Effect of Regular Exercise on Inflammation Induced by Drug-resistant Staphylococcus aureus 3089 in ICR mice
Lee, J., Luchian, T., & Park, Y. (2015) · Scientific Reports · doi:10.1038/srep16364 · Cited by 7
Sweet Bee Venom Triggers Multiple Cell Death Pathways or Spurs Acute Cell Rupture According to Its Concentration in THP-1 Monocytic Leukemia Cells
Ryu, J.-M., Na, H.-H., Park, Y.-J., Park, J.-S., Ahn, B.-S., & Kim, K. (2022) · Genes · doi:10.3390/genes13020223 · Cited by 7
“Several previous papers have suggested that cytokines could inhibit cancer cell survival development and progression [44,45].”
Background
Skeletal Muscle as Endocrine Organ
Ma, M., Zhang, Z., Hai, B., & Zhang, Y. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-88361-3_22 · Cited by 9
Impact of skeletal muscle mass on postoperative complications in oral cancer surgery
Fujii, A., Suzuki, T., Sakai, K., Matsuura, N., Sugahara, K., Katakura, A., & Nomura, T. (2024) · Maxillofacial Plastic and Reconstructive Surgery · doi:10.1186/s40902-024-00417-w · Cited by 6
“Hojman et al. reported that myokines, which are released from muscles during exercise, inhibit the growth of breast cancer cells and induce apoptosis of these cells [38].”
Background
Role of exercise on the reduction of cancer development: a mechanistic review from the lncRNA point of view
Liu, Q. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01618-x · Cited by 6
Myokines derived from contracting skeletal muscle suppress anabolism in MCF7 breast cancer cells by inhibiting mTOR
Davis, A. R., Goodenough, C. G., Westerlind, K. C., Strange, R., Deaver, J. W., Ryan, P. J., Riechman, S. E., & Fluckey, J. D. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1033585 · Cited by 6
Muscle-derived exosomes and exercise in cancer prevention
Vitucci, D., Martone, D., Alfieri, A., & Buono, P. (2023) · Frontiers in Molecular Medicine · doi:10.3389/fmmed.2023.1202190 · Cited by 7
“It can act as a tumour suppressor, both by influencing several distinctive features of cancer cells (Hojman et al., 2011; Ruiz-Casado et al., 2017) and by inducing changes in the metabolic activity of tumour cells (Pedersen and Saltin, 2015).”
Background
Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6
Wang, D., Zhang, H.-X., Yan, G.-J., Zhao, H.-R., Dong, X.-H., Tan, Y., Li, S., Lu, M., Mei, R., Liu, L.-N., et al. (2023) · Experimental Brain Research · doi:10.1007/s00221-023-06734-2 · Cited by 6
“The mice from the Runners or Non-Runners group were sacrificed to obtain exercise-(R) or non-exercise-conditioned (NRs) serum ( n = 9) (Hojman et al. 2011).”
Method
Skeletal Muscle-Derived Irisin Enhances Gemcitabine Sensitivity and Suppresses Migration Ability in Pancreatic Ductal Adenocarcinoma
Sugimoto, T., Iwagami, Y., Kobayashi, S., Yamanaka, C., Sasaki, K., Yamada, D., Tomimaru, Y., Asaoka, T., Noda, T., Takahashi, H., et al. (2024) · Annals of Surgical Oncology · doi:10.1245/s10434-024-15118-x · Cited by 6
“18 However, no previous reports investigated the anticancer effects of myokines in PDAC treated with NAC.”
Oncostatin M: Risks and Benefits of a Novel Therapeutic Target for Atherosclerosis
Venhorst, J., Rankouhi, T. R., van Keulen, D., & Tempel, D. (2022) · Current Drug Targets · doi:10.2174/1389450123666220811101032 · Cited by 6
TOMOGRAPHIC SARCOPENIA PREDICTS ANASTOMOTIC LEAKS AND LONG-TERM SURVIVAL IN GASTRIC CANCER PATIENTS OPERATED WITH CURATIVE INTENT
Figueroa, M., Araya, F., TORREALBA, A., Jose Weisz, C., Enrique Lanzarini, S., Musleh, M., Molina, J. C., Owen Korn, B., Braghetto, I., & Csendes, A. (2023) · ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) · doi:10.1590/0102-672020230002e1723 · Cited by 7
Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease
Casso-Chapa, B., González, N. A. V., Le, N., Palaskas, N. L., Nead, K. T., Eutsey, L. P., Samanthapudi, V. S. K., Osborn, A. M., Lee, J., Mejia, G. F., et al. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.319870 · Cited by 5
Physical activity and exercise in liver cancer
Chen, H., Zhou, H., Wu, B., Lu, H., Zhang, J., Zhang, Y., Gu, Y., Guangwen, Z., Xiang, J., & Yang, J. (2024) · Liver Research · doi:10.1016/j.livres.2024.03.001 · Cited by 5
Single and consecutive 10-day remote ischemic preconditioning modify physical performance, post-exercise exerkine levels, and inflammation
Kochanowicz, M., Brzezinska, P. B., Mieszkowski, J., Kochanowicz, A., Niespodziński, B., Surmiak, M., Reczkowicz, J., Borkowska, A., & Antosiewicz, J. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1428404 · Cited by 5
Can high-intensity interval training impact tumor suppression and inflammatory response in prostate cancer survivors?
Gresham, G. K., Raines, C., Asher, A., Freedland, S. J., Shirazipour, C. H., & Sleight, A. G. (2023) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-023-00661-7 · Cited by 5
Characteristics of Skeletal Muscle as a Secretory Organ
Aoi, W. (2017) · Springer eBooks · doi:10.1007/978-981-10-3292-9_9 · Cited by 5
Lifestyle and Cancer Prevention
Basen‐Engquist, K., Brown, P. H., Coletta, A. M., Savage, M. I., Maresso, K. C., & Hawk, E. T. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-47674-4.00022-0 · Cited by 5
The role of exercise-induced myokines in cancer-associated inflammation and immune regulation: mechanisms and prospects
Li, A., Sun, R., Wu, Y., Zhang, Q., Mao, R., Sun, X.-D., Wang, L., & Ren, X.-Y. (2026) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2026.1768179 · Cited by 5
“In a rat model, treadmill training signiﬁcantly prolonged tumor latency in breast cancer rats, while blocking its function with anti-OSM antibodies reversed the protective effect of exercise (65).”
Myokines related to leukocyte recruitment are down-regulated in osteosarcoma
Yu, M., Hu, B., Wang, Q., Yang, Q., & Zhou, S. (2018) · International Journal of Medical Sciences · doi:10.7150/ijms.24928 · Cited by 4
“More importantly, many studies have revealed the role of some individual myokines in various type of cancers, such as breast cancer, prostate cancer and so on [26-28].”
Background
Exercise role in improving the immune system and physical fitness during Corona pandemic period and associated exercise guidelines
Ahmadizad, S., & Bassami, M. (2020) · Journal of Sport and Exercise Physiology · doi:10.52547/joeppa.13.1.1 · Cited by 4
Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer
Peng, H., Wu, X., Wen, Y., Ao, Y., Li, Y., Guan, W., Lin, J., Li, C., Liang, H., He, J., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.742718 · Cited by 4
“The downregulation of anti-cancer responses may be a key activator for the inflammatory pathways characterized by the elevated concentrations of CRP, which are important for the development of several malignancies (Hojman et al., 2011; Pedersen and Febbraio, 2012; Aoi et al., 2013).”
Background
Muscle-to-organ cross-talk mediated by interleukin 6 during exercise: a review
Rad, R. S., & Panahzadeh, F. (2023) · Sport Sciences for Health · doi:10.1007/s11332-023-01102-7 · Cited by 5
“…suggested the involvement of various myokines, including Oncostatin M, irisin, and SPARC, in inhibiting the growth of breast and colon cancer [104, 108–111] Multiple physiologic and metabolic effects of exercise-induced IL-6 on appetite, lipid and glucose metabolism, browning of white fat, bone…”
Immune Function, Nutrition, and Exercise
Aoi, W., Naito, Y., & Yoshikawa, T. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-396454-0.00008-4 · Cited by 4
Myokines and Metabolism
Pedersen, B. K. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_31 · Cited by 4
The process to overcome lung cancer sarcopenia
Kawaguchi, Y. (2023) · Journal of Thoracic Disease · doi:10.21037/jtd-2023-01 · Cited by 4
“For example, muscle-derived myokines, such as Oncostatin M, Irisin, SPARC, IL-6, inhibit the growth of cancer cells in vitro (7,8).”
Exercise-secreted antitumor myokines: mechanistic insights and translational potential
Han, S., Du, C., Zhao, C., Zhang, Q., Wu, M., Yang, C., & Liu, X. (2026) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2026.1830759 · Cited by 3
“Neutralization with OSM-speciﬁc antibodies reduced caspase activity by 51%, further conﬁrming OSM’s role in mediating exercise-related antitumor effects (16).”
The potential role of exercise in mitigating fertility toxicity associated with immune checkpoint inhibitors (ICIs) in cancer patients
Jamrasi, P., Tazi, M., Zulkifli, N. A. B., Bae, J. H., & Song, W. J. (2024) · The Journal of Physiological Sciences · doi:10.1186/s12576-024-00950-3 · Cited by 3
“Several myokines, including IL-6, irisin, oncostatin M (OSM), secreted protein acidic and rich in cysteine (SPARC), and decorin, which increase during exercise, play critical roles in cancer suppression by reducing cell proliferation, promoting apoptosis, and inhibiting metastasis [14, 71, 72].”
Randomized pilot study of an individualized multimodal exercise, nutrition, and behavior intervention in breast cancer patients treated with ovarian function suppression: protocol proposal for The OvS Breast ENBI Project
López, B. H., Montealegre, M. C., Soulas, C., Rufrancos, B. A., Cuéllar, M. L. G.-O., Millán, M. D. M., Villarejo, L., Cobo, S. L.-T., Gilarranz, Y. J., Díaz-Guardamino, I. E., et al. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1622622 · Cited by 3
Aging Immunity and the Impact of Physical Exercise
Bigley, A. B., Baker, F. L., Spielmann, G., & Simpson, R. J. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_165 · Cited by 3
Effects of exercise training on prostate cancer: Current evidence and potential molecular mechanisms
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Exercise and tumor proteome: insights from a neuroblastoma model
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Run for your life: an integrated virtual tissue platform for incorporating exercise oncology into immunotherapy
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Effects of exercise on circulating levels of sex hormones in overweight and obese postmenopausal women: A systematic review
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“Furthermore, pre-clinical in vivo and in vitro studies have reported that endurance exercise can inhibit tumor incidence, growth and metastasis [10], [11].”
Background
Prognostic significance of the cachexia index for patients with perihilar cholangiocarcinoma
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Effects of acute exercise on inflammatory and metabolic biomarkers in women: a randomized controlled trial
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Exercise-induced modulation of circulating and exosomal microRNAs and long non-coding RNAs: Molecular signatures in cancer diagnosis, prevention and therapy
Wang, Z., Chen, Q., & Choi, K. H. (2025) · Clinica Chimica Acta · doi:10.1016/j.cca.2025.120737 · Cited by 2

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)
ORCID: Brandt, Claus
Pedersen, Line
Pedersen, Bente Klarlund
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
DOI: 10.1152/ajpendo.00520.2010
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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Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth

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