{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:38:18Z","timestamp":1778254698192,"version":"3.51.4"},"posted":{"date-parts":[[2025,1,27]]},"group-title":"Physiology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Stretching exercises such as yoga are recommended for cancer survivors to manage symptoms and promote wellbeing in clinical settings. Although other types of exercise (e.g. running) can reduce the growth of tumors in animal models, the role of stretching on tumor growth remains unclear, and the lack of a preclinical self-stretching model has impeded mechanistic studies on health benefits of stretching. We sought to develop a voluntary stretching animal model to address this research gap and apply it to breast cancer research.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using food, water, and enrichment in the home cage as motivators for stretching, a two-week 24\/7 behavior monitoring was conducted in a video-based customizable home-cage behavior tracking system, Noldus PhenoTyper, to promote self-stretching in FVB mice. Subsequently, this model was utilized in a comparative study of voluntary stretching and voluntary running on tumor growth and plasma protein profiles in the MET-1 orthotopic mammary tumor FVB mouse model.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The new voluntary stretching model effectively elicited mouse self-stretching in the custom cage setting in the long-term observation and significantly inhibited tumor growth as effectively as voluntary wheel running. Moreover, plasma proteomic analysis demonstrated that voluntary stretch versus voluntary running distinctly impacted systemic protein profiles, possibly linking to different cellular and molecular mechanisms underlying anti-cancer effects and, potentially, exercise-induced benefits in other health conditions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our work provides the first preclinical voluntary stretching model, which may be well suited to breast cancer research and a valuable research tool to facilitate investigations of stretching health benefits across various research fields.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.24.634735","type":"posted-content","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T13:40:30Z","timestamp":1737985230000},"source":"Crossref","is-referenced-by-count":1,"title":["A novel mouse model of voluntary stretching and its application in breast cancer research"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-0565","authenticated-orcid":false,"given":"Yi","family":"He","sequence":"first","affiliation":[{"name":"Connective Tissue Section, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-6448","authenticated-orcid":false,"given":"Lisbeth","family":"Berrueta","sequence":"additional","affiliation":[{"name":"Connective Tissue Section, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-9527","authenticated-orcid":false,"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Facility, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda 20892, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary J.","family":"Badger","sequence":"additional","affiliation":[{"name":"Department of Medical Biostatistics, University of Vermont, Burlington, Vermont 05405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3142-1671","authenticated-orcid":false,"given":"Helene M.","family":"Langevin","sequence":"additional","affiliation":[{"name":"Connective Tissue Section, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041023000056000_2025.01.24.634735v1.1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001937"},{"key":"2026041023000056000_2025.01.24.634735v1.2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.843810"},{"key":"2026041023000056000_2025.01.24.634735v1.3","first-page":"378","article-title":"Pre-tumor exercise decreases breast cancer in old mice in a distance-dependent manner","volume":"4","year":"2014","journal-title":"Am J Cancer Res"},{"key":"2026041023000056000_2025.01.24.634735v1.4","doi-asserted-by":"crossref","unstructured":"Goh J , Tsai J , Bammler TK , Farin FM , Endicott E , Ladiges WC . Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner. Plos One 2013;8.","DOI":"10.1371\/journal.pone.0080123"},{"key":"2026041023000056000_2025.01.24.634735v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00738.2017"},{"key":"2026041023000056000_2025.01.24.634735v1.6","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00424.2009"},{"key":"2026041023000056000_2025.01.24.634735v1.7","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10725"},{"key":"2026041023000056000_2025.01.24.634735v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.04.007"},{"key":"2026041023000056000_2025.01.24.634735v1.9","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-016-0419-0"},{"key":"2026041023000056000_2025.01.24.634735v1.10","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2017.22.4.260"},{"key":"2026041023000056000_2025.01.24.634735v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/BF01806628"},{"key":"2026041023000056000_2025.01.24.634735v1.12","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0b013e3283592cbb"},{"key":"2026041023000056000_2025.01.24.634735v1.13","first-page":"31","article-title":"Effects of six weeks endurance training and aloe vera supplementation on cox-2 and vegf levels in mice with breast cancer","volume":"18","year":"2017","journal-title":"Asian Pac J Cancer Prev"},{"key":"2026041023000056000_2025.01.24.634735v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2017.08.007"},{"key":"2026041023000056000_2025.01.24.634735v1.15","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00249.2009"},{"key":"2026041023000056000_2025.01.24.634735v1.16","first-page":"2720","article-title":"Effect of exercise on the induction of mammary carcinogenesis","volume":"48","year":"1988","journal-title":"Cancer Res"},{"key":"2026041023000056000_2025.01.24.634735v1.17","first-page":"1904","article-title":"Effect of type and amount of dietary fat on the enhancement of rat mammary tumorigenesis by exercise","volume":"49","year":"1989","journal-title":"Cancer Res"},{"key":"2026041023000056000_2025.01.24.634735v1.18","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e31819f1f05"},{"key":"2026041023000056000_2025.01.24.634735v1.19","first-page":"1926","article-title":"Breast cancer pulmonary metastasis is increased in mice undertaking spontaneous physical training in the running wheel; a call for revising beneficial effects of exercise on cancer progression","volume":"7","year":"2017","journal-title":"Am J Cancer Res"},{"key":"2026041023000056000_2025.01.24.634735v1.20","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11231"},{"key":"2026041023000056000_2025.01.24.634735v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116100"},{"key":"2026041023000056000_2025.01.24.634735v1.22","doi-asserted-by":"crossref","unstructured":"Gomes-Santos IL , Kumar AS , Hausmann F , et al. Exercise intensity governs tumor control in mice with breast cancer. Frontiers in Immunology 2024;15.","DOI":"10.3389\/fimmu.2024.1339232"},{"key":"2026041023000056000_2025.01.24.634735v1.23","first-page":"59","article-title":"Effect of treadmill exercise intensity on hepatic glutathione content and its relevance to mammary tumorigenesis","volume":"32","year":"1992","journal-title":"J Sports Med Phys Fitness"},{"key":"2026041023000056000_2025.01.24.634735v1.24","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.28057"},{"key":"2026041023000056000_2025.01.24.634735v1.25","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21054"},{"key":"2026041023000056000_2025.01.24.634735v1.26","first-page":"209302","article-title":"Special needs to prescribe exercise intensity for scientific studies","volume":"2011","year":"2010","journal-title":"Cardiol Res Pract"},{"key":"2026041023000056000_2025.01.24.634735v1.27","first-page":"81","article-title":"Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: A review","volume":"8","year":"2012","journal-title":"Oncol Hematol Rev"},{"key":"2026041023000056000_2025.01.24.634735v1.28","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e3181e0c112"},{"key":"2026041023000056000_2025.01.24.634735v1.29","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0000000000002116"},{"key":"2026041023000056000_2025.01.24.634735v1.30","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.1081"},{"key":"2026041023000056000_2025.01.24.634735v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctcp.2022.101581"},{"key":"2026041023000056000_2025.01.24.634735v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctcp.2019.101078"},{"key":"2026041023000056000_2025.01.24.634735v1.33","doi-asserted-by":"publisher","DOI":"10.1186\/s43161-023-00128-9"},{"key":"2026041023000056000_2025.01.24.634735v1.34","doi-asserted-by":"crossref","unstructured":"Krol M , Kupnicka P , Bosiacki M , Chlubek D . Mechanisms underlying anti-inflammatory and anti-cancer properties of stretching-a review. Int J Mol Sci 2022;23.","DOI":"10.3390\/ijms231710127"},{"key":"2026041023000056000_2025.01.24.634735v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"2026041023000056000_2025.01.24.634735v1.36","doi-asserted-by":"publisher","DOI":"10.1007\/s11845-016-1464-0"},{"key":"2026041023000056000_2025.01.24.634735v1.37","doi-asserted-by":"publisher","DOI":"10.4103\/aam.aam_56_18"},{"key":"2026041023000056000_2025.01.24.634735v1.38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0269300"},{"key":"2026041023000056000_2025.01.24.634735v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25263"},{"key":"2026041023000056000_2025.01.24.634735v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21209"},{"key":"2026041023000056000_2025.01.24.634735v1.41","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0000000000001465"},{"key":"2026041023000056000_2025.01.24.634735v1.42","first-page":"124","article-title":"Stretching reduces skin thickness and improves subcutaneous tissue mobility in a murine model of systemic sclerosis","volume":"8","year":"2017","journal-title":"Front Immunol"},{"key":"2026041023000056000_2025.01.24.634735v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26198-7"},{"key":"2026041023000056000_2025.01.24.634735v1.44","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.Rs-2042475\/v1"},{"key":"2026041023000056000_2025.01.24.634735v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-56860-7"},{"key":"2026041023000056000_2025.01.24.634735v1.46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179588"},{"key":"2026041023000056000_2025.01.24.634735v1.47","unstructured":"Society AP . Resource book for the design of animal exercise protocols. American Physiological Society; 2006."},{"key":"2026041023000056000_2025.01.24.634735v1.48","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2016.20.3.287"},{"key":"2026041023000056000_2025.01.24.634735v1.49","doi-asserted-by":"crossref","unstructured":"Tang DD , Chen MJ , Huang XH , et al. Srplot: A free online platform for data visualization and graphing. Plos One 2023;18.","DOI":"10.1371\/journal.pone.0294236"},{"key":"2026041023000056000_2025.01.24.634735v1.50","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAC194"},{"key":"2026041023000056000_2025.01.24.634735v1.51","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.27.9935"},{"key":"2026041023000056000_2025.01.24.634735v1.52","doi-asserted-by":"publisher","DOI":"10.1097\/00008469-199904000-00002"},{"key":"2026041023000056000_2025.01.24.634735v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2011.12.012"},{"key":"2026041023000056000_2025.01.24.634735v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2018.06.011"},{"key":"2026041023000056000_2025.01.24.634735v1.55","unstructured":"Physical activity guidelines for americans, 2nd edition. Washington, DC: U.S. Department of Health and Human Services; 2018."},{"key":"2026041023000056000_2025.01.24.634735v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-4307-9_4"},{"key":"2026041023000056000_2025.01.24.634735v1.57","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1496-0"},{"key":"2026041023000056000_2025.01.24.634735v1.58","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-023-01898-x"},{"key":"2026041023000056000_2025.01.24.634735v1.59","doi-asserted-by":"publisher","DOI":"10.2519\/jospt.2002.32.2.36"},{"key":"2026041023000056000_2025.01.24.634735v1.60","doi-asserted-by":"crossref","unstructured":"Can A , Dao DT , Terrillion CE , Piantadosi SC , Gould TD , Bhat S. The tail suspension test. JoVE 2012:e3769.","DOI":"10.3791\/3769-v"},{"key":"2026041023000056000_2025.01.24.634735v1.61","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8994-2_16"},{"key":"2026041023000056000_2025.01.24.634735v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.009"},{"key":"2026041023000056000_2025.01.24.634735v1.63","doi-asserted-by":"publisher","DOI":"10.34117\/bjdv6n9-578"},{"key":"2026041023000056000_2025.01.24.634735v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2016.09.002"},{"key":"2026041023000056000_2025.01.24.634735v1.65","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-07804-w"},{"key":"2026041023000056000_2025.01.24.634735v1.66","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6387"},{"key":"2026041023000056000_2025.01.24.634735v1.67","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1249\/MSS.0000000000001446","article-title":"Exercise prescription and adherence for breast cancer: One size does not fitt all","volume":"50","year":"2018","journal-title":"Med Sci Sports Exerc"},{"key":"2026041023000056000_2025.01.24.634735v1.68","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-005-9067-5"},{"key":"2026041023000056000_2025.01.24.634735v1.69","doi-asserted-by":"publisher","DOI":"10.1016\/0889-1591(91)90016-4"},{"key":"2026041023000056000_2025.01.24.634735v1.70","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02223-y"},{"key":"2026041023000056000_2025.01.24.634735v1.71","doi-asserted-by":"crossref","unstructured":"Nehme R , Diab-Assaf M , Decombat C , Delort L , Caldefie-Chezet F . Targeting adiponectin in breast cancer. Biomedicines 2022;10.","DOI":"10.3390\/biomedicines10112958"},{"key":"2026041023000056000_2025.01.24.634735v1.72","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_1091_19"},{"key":"2026041023000056000_2025.01.24.634735v1.73","doi-asserted-by":"publisher","DOI":"10.5152\/ejbh.2018.4349"},{"key":"2026041023000056000_2025.01.24.634735v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2023.102032"},{"key":"2026041023000056000_2025.01.24.634735v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnha.2023.100005"},{"key":"2026041023000056000_2025.01.24.634735v1.76","doi-asserted-by":"publisher","DOI":"10.1002\/msc.1576"},{"key":"2026041023000056000_2025.01.24.634735v1.77","doi-asserted-by":"publisher","DOI":"10.1007\/s10865-018-9914-y"},{"key":"2026041023000056000_2025.01.24.634735v1.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2013.05.013"},{"key":"2026041023000056000_2025.01.24.634735v1.79","doi-asserted-by":"crossref","unstructured":"Luxem K , Sun JJ , Bradley SP , et al. Open-source tools for behavioral video analysis: Setup, methods, and best practices. Elife 2023;12.","DOI":"10.7554\/eLife.79305"},{"key":"2026041023000056000_2025.01.24.634735v1.80","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0396-1"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.01.24.634735","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:00:13Z","timestamp":1775887213000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.01.24.634735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":80,"URL":"https:\/\/doi.org\/10.1101\/2025.01.24.634735","relation":{},"subject":[],"published":{"date-parts":[[2025,1,27]]},"subtype":"preprint"}}