The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388
Insulin and insulin-like growth factor signalling in neoplasia
Pollak, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2536 · Cited by 2,059
Tumour necrosis factor and cancer
Balkwill, F. R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2628 · Cited by 1,976
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A. M., & Karin, M. (2007) · Science · doi:10.1126/science.1140485 · Cited by 1,955
Steensberg, A., van Hall, G., Osada, T., Sacchetti, M., Saltin, B., & Pedersen, B. K. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00237.x · Cited by 1,095
Mechanisms linking physical activity with cancer
McTiernan, A. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2325 · Cited by 743
Matthews, V. B., Åström, M.-B., Chan, M. H. S., Bruce, C. R., Krabbe, K. S., Prelovsek, O., Åkerström, T., Yfanti, C., Broholm, C., Mortensen, O. H., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1364-1 · Cited by 722 · cited 1×
“, as mediators of muscle-to-fat cross-talk and in controlling muscular glucose and fat metabolism (9, 14, 19, 22).”
BackgroundEvidence that interleukin-6 is produced in human skeletal muscle during prolonged running
Ostrowski, K., Rohde, T., Zacho, M., Asp, S., & Pedersen, B. K. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.949bp.x · Cited by 673
The diseasome of physical inactivity – and the role of myokines in muscle–fat cross talk
Pedersen, B. K. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179515 · Cited by 631
Flagged first, then by citations
Research works printed but not linked: 5
- Davis AR, 2009, 14th International Conference Biochemistry of Exercise (Abstract no. 30)
- Hutt JA, 2002, Mol Cancer Ther, 1, 601
- Liu J, 1999, Cell Growth Diff, 10, 677
- Soliman S, Evid Based Complement Alternat Med
- World Cancer Research Fund and American Institute of Cancer Research, 2007, Food, Nutrition, Physical Activity, and the Prevention of Cancer
Cited by
Sorted by citations
Items 201–256 of 256
Exercise-derived extracellular vesicles in oncology: a new frontier for translational nanomedicine
Silvestri, M., Fantini, C., Duranti, G., Grazioli, E., Caporossi, D., Balbi, C., & Dimauro, I. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07742-w · Cited by 3
Chen, Q., Lü, J., Lu, X., Yao, X., Zhang, X.-P., Wang, S.-Y., & Guo, J. (2022) · Frontiers in Surgery · doi:10.3389/fsurg.2022.852137 · Cited by 2
Exercise therapy: Anti-tumor and improving chemotherapy efficacy
Wang, Z., Wang, Z., Chen, H., Siyuan, L., Yang, J., Ma, Y., Zhou, C., Jin, X., Liu, J., & Wang, X. (2024) · Journal of Holistic Integrative Pharmacy · doi:10.1016/j.jhip.2024.09.001 · Cited by 2
Shibutani, M., Tanda, H., Seki, Y., Kashiwagi, S., Nishiyama, T., Fukui, Y., Imanishi, D., Kasashima, H., Fukuoka, T., & Maeda, K. (2024) · Scientific Reports · doi:10.1038/s41598-024-77766-z · Cited by 2
“Furthermore, myokines released from skeletal muscle and exerting antitumor effects may be reduced in patients with cancer cachexia, because patients with cancer cachexia often have a reduced skeletal muscle mass 16,17 .”
BackgroundMultidisciplinary perspectives in exercise oncology across the translational research continuum
Courneya, K. S., Lucía, A., May, A. M., Rundqvist, H., & Rogers, L. Q. (2025) · JNCI Monographs · doi:10.1093/jncimonographs/lgaf032 · Cited by 2
Tanda, H., Shibutani, M., Seki, Y., Nishiyama, T., Kasashima, H., Fukuoka, T., & Maeda, K. (2025) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-025-01320-x · Cited by 2
“The skeletal muscle also functions as an endocrine organ [13], and cytokines released from the muscles are called myokines, which play an important role in the interaction between skeletal muscle and tumors and are believed to regulate tumor promotion [14, 15].”
Masik, N. P., & Kalandey, K. Y. (2019) · PAIN JOINTS SPINE · doi:10.22141/2224-1507.9.2.2019.172123 · Cited by 2
“Myokine, having the antiproliferative effect, was identified as oncostatin M [25].”
BackgroundAoi, W. (2013) · 体力科學 · doi:10.7600/jspfsm.62.263 · Cited by 2
Barbieri, E., Falcieri, E., Santi, M. D., Natalucci, V., Vallorani, L., Agostini, D., Annibalini, G., Stefani, L., Szychlinska, M. A., & Musumeci, G. (2018) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk3020023 · Cited by 2
“For example, in response to exercise-conditioned serum treatment, BC cell growth is inhibited by 10–15% compared to tumor growth observed in the control setting, but there is not a complete eradication of cancer cells [17,18].”
BackgroundMechanisms of Exercise in Cancer Prevention, Treatment, and Survivorship
Savage, H., & Schadler, K. (2020) · Springer eBooks · doi:10.1007/978-3-030-42011-6_4 · Cited by 2
The effects of heat stress in redox balance and inflammatory signaling in porcine skeletal muscle
Montilla, S. I. R. (2013) · doi:10.31274/etd-180810-3132 · Cited by 2
“Finally, increased superoxide production (35-37) from heat stressed mitochondria isolated from avian skeletal muscle was previously reported along with associated changes in uncoupling protein expression (35) raising the possibility of a similar mechanism in mammalian skeletal muscle.”
BackgroundResultInfluentialLerner, U. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11553-3 · Cited by 2
Myokine Expression in Cancer Cachexia
Manole, E., Ceafalan, L. C., Gaina, G. F., Mosoia, O., & Hinescu, M. E. (2023) · Interdisciplinary cancer research · doi:10.1007/16833_2023_138 · Cited by 1
Exercise in patients with metastatic prostate cancer: A comprehensive review
Carrillo, F. J. M. I., de Herreros, M. G., Carrillo, D., Peralta, O., Aversa, C., Fernández-Mañas, L., Ferrer‐Mileo, L., Altamirano, M. F. A., Torras, Ò. R., Jiménez, N., et al. (2025) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2025.102996 · Cited by 2
Breast Tumor Blood Flow, Disease Progression, and Treatment Response: The Role of Exercise
Ruberti, O. M., Telles, G. D., Derchain, S., Araújo, R. B., Lima, D., Bortolozo, H. I., Sarian, L. O., Zopf, E. M., Jales, R. M., & Conceição, M. S. (2026) · Sports Medicine · doi:10.1007/s40279-026-02392-w · Cited by 2
“Also, Hojman et al. identified oncostatin M (OSM) in exercise-conditioned serum and muscle-derived media as a key myokine mediating the inhibitory effects of exercise on mammary cancer cell growth [62].”
Morales, J. S., Lucía, A., & Pareja-Galeano, H. (2016) · ABACUS. Repositorio de Producción Científica (Universidad Europea) · Cited by 1
Association of Physical Activity level with the COVID-19 Incidence in Patients with Type 2 Diabetes
Hoseini, R., Hoseini, Z., Bahmani, E., & Darmian, M. A. (2022) · Journal of Advances in Medical and Biomedical Research · doi:10.30699/jambs.30.143.513 · Cited by 1
“Thus, regular moderate-intensity exercise might improve or maintain the immune system response to infections positively (34, 35).”
BackgroundExercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M
Yoshimura, T., Hirano, Y., Hamada, T., Yokoyama, S., Suzuki, H., Takayama, H., Migita, H., Ishida, T., Nakamura, Y., Ohsawa, M., et al. (2024) · Cancers · doi:10.3390/cancers16061187 · Cited by 1
Pedersen, B. K. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_31-1 · Cited by 1
The Effects of Long-term Exercise on the Expression of SPARC and OSM in Colon Cancer-induced Mice
Kim, J., Cho, E.-H., & Jeon, T.-W. (2016) · Exercise Science · doi:10.15857/ksep.2016.25.2.76 · Cited by 1
“OSM은 항암 효과를 일으키는 역할로 잘 알려져 있는데, 특히 유방 암 세포로 알려진 MCF-7에 있어 의존적(dose-dependent) 효과가 있다 고 알려져 있고[54], 이는 Transcriptional suppression of synuclein gamma (SNCG) 발현을 통한 종양세포 증식 억제와[52,55], p53, caspase 등 의 작용을 통한 종양 세포의 자멸(apoptosis)을 일으키는 것으로 알려 져 있다[5].”
InfluentialBórquez, J. C., Montes, N., & Díaz-Bautista, E. (2018) · Revista médica de Chile · doi:10.4067/s0034-98872018000600762 · Cited by 2
Exercise-Induced Chaperokine Activity of Hsp70: Possible Role in Chronic Diseases
Shamsi, M. M., Hassan, Z. M., & Gharakhanlou, R. (2019) · Heat shock proteins · doi:10.1007/978-3-030-02254-9_10 · Cited by 2
Ingenious function of skeletal muscle as a secretory organ: Its crucial role for cancer prevention
Aoi, W. (2014) · The Journal of Physical Fitness and Sports Medicine · doi:10.7600/jpfsm.3.211
Exercise and adipose tissue GLUT4
Opazo, F., & Alejandro, M. (2017) · Minerva Access (University of Melbourne)
Ernährung und Bewegung: Die Bedeutung der Lebensführung für Krebs
Kleeberg, U. R. (2018) · Deutsche Zeitschrift für Onkologie · doi:10.1055/a-0635-2899
Vulczak, A. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.22.2019.tde-27032019-155119
How to Treat or Prevent, or Slow Down, Cellular Ageing and Senescence?
Swynghedauw, B. (2019) · Practical issues in geriatrics · doi:10.1007/978-3-030-15111-9_7
The Effects of Acute Exercise and Aging on the Growth of Prostate Cancer Cells
Hwang, J. H. (2019) · Queensland University of Technology · doi:10.5204/thesis.eprints.130703
Efeito do treinamento físico na função cardíaca e no fenótipo muscular estriado em câncer de mama
da Costa, T. S. R. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2020.tde-09072020-141948
The Role of Exercise and Physical Activity against COVID-19: A Narrative Review Study
Heidary, D., & Mehdipour, A. (2021) · Depiction of Health · doi:10.34172/doh.2021.28
Aging Immunity and the Impact of Physical Exercise
Bigley, A. B., Baker, F. L., Spielmann, G., & Simpson, R. J. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_165-1
The Association Between Physical Activity Level of CVD Patients and Rate of Covid-19 Incidence
Hoseini, R., Hoseini, Z., Bahmani, E., & Darmian, M. A. (2022) · International Journal of Infection · doi:10.5812/iji.118853
Novel Therapeutic Strategy for the Prevention of Bone Fractures
Hamrick, M. W. (2014) · Defense Technical Information Center (DTIC) · doi:10.21236/ada614236
Physical Activity in Patients with Breast Cancer
Saito, T., & Ono, R. (2022) · Springer eBooks · doi:10.1007/978-981-19-6710-8_13
Seok, H., Shim, E., Jung, M., Kim, J., Jeon, J. H., Choi, W. S., & Park, D. W. (2023) · Research Square · doi:10.21203/rs.3.rs-2525054/v1
Fujii, A., Suzuki, T., Sakai, K., Matsuura, N., Sugahara, K., Katakura, A., & Nomura, T. (2023) · Research Square · doi:10.21203/rs.3.rs-3265340/v1
Hajinajaf, S., Shirvani, H., Roozbahani, M., & Khademi, A. (2023) · مجله علمی پزشکی جندی شاپور · doi:10.32598/jsmj.21.6.2825
Exercise and Energy Metabolism in Cancer Research
Vulczak, A., & Alberici, L. C. (2024) · Interdisciplinary cancer research · doi:10.1007/16833_2024_228
Holtorf, C., Mengoni, M., Tüting, T., Wienke, A., Borggrefe, J., Surov, A., & Alter, M. (2024) · Die Dermatologie · doi:10.1007/s00105-024-05405-9
Vela, V., Sabani, B., & Spahn, G. (2025) · Springer eBooks · doi:10.1007/978-3-031-84297-9_9
Körperliche Aktivität und Krebs
Vela, V., & Spahn, G. (2025) · Springer eBooks · doi:10.1007/978-3-662-70291-8_9
Ye, K., Ke, Z., Gesang, W., Liang, K., & Malek, M. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03950-4
“Although most studies have focused on breast and colon cancers, similar mechanisms may influence prostate cancer development through systemic and localized effects [28, 29].”
de Luis, D. A., Primo, D., Izaola, O., & Gómez, J. J. L. (2025) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2025.501677
Wang, M., Zhang, Z., Zhang, X., Dai, R., Wang, Z., Chen, Z., Lei, L., Li, Z., & Guo, Q. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169535
Ma, Z., Lin, Y., Zhang, B., Yue, P., Li, B., & Meng, W. (2025) · Scientific Reports · doi:10.1038/s41598-025-30485-5
de Luis, D., Primo, D., Izaola, O., & Lopez-Gomez, J. J. (2026) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2025.501677
Pozharashka, J., Bozhilova, R., Hristova, M. H., Kamenarska, Z. G., Kalinova, D., Vinkov, A. I., Kaneva, R. P., Kolarov, Z., & Dourmishev, L. (2026) · Acta Medica Bulgarica · doi:10.2478/amb-2026-0039
川口, 庸., 花岡, 淳., 大塩, 恭., 岡本, 圭., 賀来, 良., 林, 一., 白鳥, 琢., 赤澤, 彰., Kawaguchi, Y., Hanaoka, J., et al. (2021) · Institutional Repositories DataBase (IRDB)
Skeletal muscle as an endocrine and paracrine organ in breast cancer biology: a narrative review
Carpenter, D. J., Peluso, C., Xiao, K., Rosenberg, J., Lee, P. L., & Champ, C. E. (2026) · Discover Oncology · doi:10.1007/s12672-026-05027-8
“Mechanistically, myokines such as OSM, SPARC, and irisin inhibit proliferation, induce apoptosis, and modulate the tumor microenvironment in ER/PR-positive, HER2-negative cell lines (e.g., MCF-7), with OSM identified as a key mediator of exercise-induced tumor suppression [14, 15, 21].”
The relationship between sarcopenia and breast cancer: mechanistic pathways and clinical relevance
Wu, Y., Cao, H., Li, M., Hong, J., Zhou, H., Gao, X., & Song, D. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1731822
Ma, Z., Lin, Y., Zhang, B., Ma, Y., Yue, P., Yuan, J., Li, B., & Meng, W. (2026) · Scientific Reports · doi:10.1038/s41598-026-63370-w
The process to overcome lung cancer sarcopenia
川口, 庸. (2023) · Institutional Repositories DataBase (IRDB)
Artigas-Arias, M., Bonicioli, J., Huard, N., Salazar, L. A., SAPUNAR, J., Peñailillo, L., Valladares-Ide, D., Curi, R., & Marzuca-Nassr, G. N. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177900
“In this sense, it may point to regulatory pathways relevant to tumor suppression [38].”
Physical activity and breast cancer
Bugden, G., & Palmer-Quinn, K. (2026) · doi:10.71450/15254990
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
