{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:00:09Z","timestamp":1760144409221,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health","award":["3-17783"],"award-info":[{"award-number":["3-17783"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The dynamic relationship between heart failure and cancer poses a dual challenge. While cardiac remodeling can promote cancer growth and metastasis, tumor development can ameliorate cardiac dysfunction and suppress fibrosis. However, the precise mechanism through which cancer influences the heart and fibrosis is yet to be uncovered. To further explore the interaction between heart failure and cancer, we used the MDX mouse model, which suffers from cardiac fibrosis and cardiac dysfunction. A previous study from our lab demonstrated that tumor growth improves cardiac dysfunction and dampens fibrosis in the heart and diaphragm muscles of MDX mice. We used breast Polyoma middle T (PyMT) and Lewis lung carcinoma (LLC) cancer cell lines that developed into large tumors. To explore whether the aggressiveness of the cancer cell line is crucial for the beneficial phenotype, we employed a PyMT breast cancer cell line lacking integrin \u03b21, representing a less aggressive cell line compared to the original PyMT cells. In addition, we examined immortalized and primary MEF cells. The injection of integrin \u03b21 KO PyMT cancer cells and Mouse Embryo Fibroblasts cells (MEF) resulted in the improvement of cardiac function and decreased fibrosis in the heart, diaphragm, and skeletal muscles of MDX mice. Collectively, our data demonstrate that the cancer line aggressiveness as well as primary MEF cells are sufficient to impose the beneficial phenotype. These discoveries present potential novel clinical therapeutic approaches with beneficial outcome for patients with fibrotic diseases and cardiac dysfunction that do not require tumor growth.<\/jats:p>","DOI":"10.3390\/ijms25084273","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T04:44:26Z","timestamp":1712897066000},"page":"4273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardioprotection and Suppression of Fibrosis by Diverse Cancer and Non-Cancer Cell Lines in a Murine Model of Duchenne Muscular Dystrophy"],"prefix":"10.3390","volume":"25","author":[{"given":"Laris","family":"Achlaug","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Cancer Science, Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Langier Goncalves","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Cancer Science, Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-4092","authenticated-orcid":false,"given":"Ami","family":"Aronheim","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Cancer Science, Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3389\/fphys.2017.00777","article-title":"The processes and mechanisms of cardiac and pulmonary fibrosis","volume":"8","author":"Murtha","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Awwad, L., Shofti, R., Haas, T., and Aronheim, A. (2023). Tumor growth ameliorates cardiac dysfunction. Cells, 12.","DOI":"10.21203\/rs.3.rs-2345318\/v2"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Awwad, L., and Aronheim, A. (2023). Tumor Progression Reverses Cardiac Hypertrophy and Fibrosis in a Tetracycline-Regulated ATF3 Transgenic Mouse Model. 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