{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T15:14:24Z","timestamp":1761491664784,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI","award":["JP22K10152"],"award-info":[{"award-number":["JP22K10152"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0\/G1 phase, decreased the proportion of cells in the G2\/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.<\/jats:p>","DOI":"10.3390\/cancers16061187","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T05:14:07Z","timestamp":1710738847000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4564-9765","authenticated-orcid":false,"given":"Takuya","family":"Yoshimura","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-7613","authenticated-orcid":false,"given":"Taiji","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9781-6397","authenticated-orcid":false,"given":"Seiya","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-5070","authenticated-orcid":false,"given":"Hajime","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirono","family":"Migita","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunori","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Kagoshima Medical Center, National Hospital Organization, Kagoshima 892-0853, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Ohsawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharma-Science,  Laboratory of Pharmacology & Neuroscience, Teikyo University, Tokyo 252-0176, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Asakawa","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyohide","family":"Ishihata","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-1624","authenticated-orcid":false,"given":"Akihide","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.ejca.2010.02.022","article-title":"EORTC elderly task force position paper: Approach to the older cancer patient","volume":"46","author":"Pallis","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejca.2019.04.031","article-title":"Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients","volume":"116","author":"Boyle","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/jjco\/hyz093","article-title":"Geriatric research policy: Japan clinical oncology group (JCOG) policy","volume":"49","author":"Mizutani","year":"2019","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8075","DOI":"10.7314\/APJCP.2015.16.18.8075","article-title":"Sarcopenia in cancer patients","volume":"16","author":"Chindapasirt","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.11005\/jbm.2013.20.1.1","article-title":"Sarcopenia: Definition, epidemiology, and pathophysiology","volume":"20","author":"Kim","year":"2013","journal-title":"J. Bone Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.18632\/aging.100482","article-title":"Sarcopenia, obesity, and natural killer cell immune senescence in aging: Altered cytokine levels as a common mechanism","volume":"4","author":"Lutz","year":"2012","journal-title":"Aging"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, X.M., Dou, Q.L., Zeng, Y., Yang, Y., Cheng, A.S.K., and Zhang, W.W. (2020). Sarcopenia as a predictor of mortality in women with breast cancer: A meta-analysis and systematic review. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6645-6"},{"key":"ref_8","first-page":"11136","article-title":"Prognostic effect of sarcopenia in colorectal cancer recurrence","volume":"91\u201392","author":"Takiguchi","year":"2021","journal-title":"Nutrition"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s12957-020-01981-x","article-title":"Sarcopenia as a prognostic factor in patients with recurrent pancreatic cancer: A retrospective study","volume":"18","author":"Sakamoto","year":"2020","journal-title":"World J. Surg. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11882","DOI":"10.1038\/s41598-021-91449-z","article-title":"Sarcopenia is associated with poor prognosis after chemoradiotherapy in patients with stage iii non-small-cell lung cancer: A retrospective analysis","volume":"11","author":"Katsui","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yoshimura, T., Suzuki, H., Takayama, H., Higashi, S., Hirano, Y., Tezuka, M., Ishida, T., Ishihata, K., Nishi, Y., and Nakamura, Y. (2020). Impact of preoperative low prognostic nutritional index and high intramuscular adipose tissue content on outcomes of patients with oral squamous cell carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12113167"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yoshimura, T., Suzuki, H., Takayama, H., Higashi, S., Hirano, Y., Tezuka, M., Ishida, T., Ishihata, K., Nishi, Y., and Nakamura, Y. (2021). Prognostic role of preoperative sarcopenia evaluation of cervical muscles with long-term outcomes of patients with oral squamous cell carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13184725"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"812159","DOI":"10.3389\/fonc.2022.812159","article-title":"Establishment and Validation of Pre-Therapy Cervical Vertebrae Muscle Quantification as a Prognostic Marker of Sarcopenia in Patients With Head and Neck Cancer","volume":"14","author":"Olson","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_14","first-page":"159","article-title":"Effects of physical exercise in sarcopenia. A systematic review","volume":"68","author":"Vicente","year":"2021","journal-title":"Endocrinol. Diabetes Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cmet.2016.01.011","article-title":"Voluntary running suppresses tumor growth through epinephrine-and IL-6-dependent NK cell mobilization and redistribution","volume":"23","author":"Pedersen","year":"2016","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1158\/0008-5472.CAN-16-0887","article-title":"Efficacy and mechanisms of aerobic exercise on cancer initiation, progression, and metastasis: A critical systematic review of in vivo preclinical data","volume":"76","author":"Ashcraft","year":"2016","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1152\/physrev.2000.80.3.1055","article-title":"Exercise and the immune system: Regulation, integration, and adaptation","volume":"80","author":"Pedersen","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.bbi.2013.10.030","article-title":"Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells","volume":"39","author":"Bigley","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.1158\/0008-5472.CAN-16-3125","article-title":"Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer Development","volume":"77","author":"Dethlefsen","year":"2017","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.tma.2018.08.001","article-title":"The functions of sarcopenia related myokines","volume":"2","author":"Han","year":"2018","journal-title":"Transl. Med. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/bs.acc.2019.07.010","article-title":"Myokines: The endocrine coupling of skeletal muscle and bone","volume":"94","author":"Gomarasca","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41391-022-00504-x","article-title":"Exercise in advanced prostate cancer elevates myokine levels and suppresses in-vitro cell growth","volume":"25","author":"Kim","year":"2022","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41585-021-00476-y","article-title":"Exercise-induced myokines and their effect on prostate cancer","volume":"18","author":"Kim","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E197","DOI":"10.1002\/ijc.29142","article-title":"Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro","volume":"136","author":"Gannon","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"a029793","DOI":"10.1101\/cshperspect.a029793","article-title":"Skeletal muscle as an endocrine organ: The role of myokines in exercise adaptations","volume":"7","author":"Hoffmann","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3389\/fphys.2019.00042","article-title":"Role of myokines in regulating skeletal muscle mass and function","volume":"10","author":"Lee","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_27","first-page":"1583","article-title":"Myokines: A descriptive review","volume":"60","author":"Barbalho","year":"2020","journal-title":"J. Sports Med. Phys. Fit."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107158","DOI":"10.1016\/j.intimp.2020.107158","article-title":"Oncostatin M: A mysterious cytokine in cancers","volume":"90","author":"Masjedi","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1023\/A:1010614724664","article-title":"Oncostatin M-induced growth inhibition and morphological changes of MDA-MB231 breast cancer cells are abolished by blocking the MEK\/ERK signaling pathway","volume":"66","author":"Li","year":"2001","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60395","DOI":"10.18632\/oncotarget.10939","article-title":"Oncostatin M suppresses metastasis of lung adenocarcinoma by inhibiting SLUG expression through coordination of STATs and PIASs signalings","volume":"7","author":"Pan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1002\/ijc.25776","article-title":"Direct anti-cancer effect of oncostatin M on chondrosarcoma","volume":"128","author":"David","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chuerduangphui, J., Ekalaksananan, T., Chaiyarit, P., Patarapadungkit, N., Chotiyano, A., Kongyingyoes, B., Promthet, S., and Pientong, C. (2018). Effects of arecoline on proliferation of oral squamous cell carcinoma cells by dysregulating c-Myc and miR-22, directly targeting oncostatin M. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192009"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5468","DOI":"10.18632\/oncotarget.27189","article-title":"One-bead one-compound combinatorial library derived targeting ligands for detection and treatment of oral squamous cancer","volume":"10","author":"Yang","year":"2019","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1038\/s41598-022-08850-5","article-title":"Exercise suppresses tumor growth independent of high fat food intake and associated immune dysfunction","volume":"12","author":"Hojman","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.jhep.2015.01.017","article-title":"Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis","volume":"62","author":"Piguet","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1158\/2326-6066.CIR-20-0499","article-title":"Exercise Training Improves Tumor Control by Increasing CD8+ T-cell Infiltration via CXCR3 Signaling and Sensitizes Breast Cancer to Immune Checkpoint Blockade","volume":"9","author":"Amoozgar","year":"2021","journal-title":"Cancer Immunol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.prp.2012.04.006","article-title":"The influence of physical activity in the progression of experimental lung cancer in mice","volume":"208","author":"Paceli","year":"2012","journal-title":"Pathol. Res. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1007\/s11845-021-02785-y","article-title":"The effect of exercise on disease-free survival and overall survival in patients with breast cancer","volume":"191","author":"Akdeniz","year":"2022","journal-title":"Ir. J. Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1096\/fj.14-263699","article-title":"The search for exercise factors in humans","volume":"29","author":"Catoire","year":"2015","journal-title":"FASEB J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E504","DOI":"10.1152\/ajpendo.00520.2010","article-title":"Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth","volume":"301","author":"Hojman","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/s41391-022-00624-4","article-title":"Acute effect of high-intensity interval aerobic exercise on serum myokine levels and resulting tumour-suppressive effect in trained patients with advanced prostate cancer","volume":"26","author":"Kim","year":"2023","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yang, W., Liu, Y., Yang, G., Meng, B., Yi, Z., Yang, G., Chen, M., Hou, P., Wang, H., and Xu, X. (2021). Moderate-Intensity Physical Exercise Affects the Exercise Performance and Gut Microbiota of Mice. Front. Cell. Infect. Microbiol., 24.","DOI":"10.3389\/fcimb.2021.712381"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/6\/1187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:16Z","timestamp":1760105716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/6\/1187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["cancers16061187"],"URL":"https:\/\/doi.org\/10.3390\/cancers16061187","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2024,3,18]]}}}