{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:51:46Z","timestamp":1792183906102,"version":"4.4.0"},"reference-count":101,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO3CA227359"],"award-info":[{"award-number":["RO3CA227359"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["P30 CA16852"],"award-info":[{"award-number":["P30 CA16852"]}]},{"name":"National Cancer Institute","award":["R37CA218118"],"award-info":[{"award-number":["R37CA218118"]}]},{"DOI":"10.13039\/100007859","name":"University of Kansas","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007859","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Despite advancements in treatment, approximately 25% of patients with breast cancer experience long-term skeletal muscle wasting (SMW), which limits mobility, reduces drug tolerance and adversely impacts survival. By understanding the underlying molecular mechanisms of SMW, we may be able to develop new strategies to alleviate this condition and improve the lives of patients with breast cancer. Chemokines are small soluble factors that regulate homing of immune cells to tissues during inflammation. In breast cancers, overexpression of C-C chemokine ligand 2 (CCL2) correlates with unfavorable prognosis. Elevated levels of CCL2 in peripheral blood indicate possible systemic effects of this chemokine in patients with breast cancer. Here, we investigated the role of CCL2 signaling on SMW in tumor and non-tumor contexts. In vitro, increasing concentrations of CCL2 inhibited myoblast and myotube function through C-C chemokine receptor 2 (CCR2)-dependent mechanisms involving JNK, SMAD3 and AMPK signaling. In healthy mice, delivery of recombinant CCL2 protein promoted SMW in a dose-dependent manner. In vivo knockdown of breast tumor-derived CCL2 partially protected against SMW. Overall, chronic, upregulated CCL2\u2013CCR2 signaling positively regulates SMW, with implications for therapeutic targeting.<\/jats:p>","DOI":"10.1242\/dmm.050398","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T08:25:06Z","timestamp":1720427106000},"source":"Crossref","is-referenced-by-count":10,"title":["CCL2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor models"],"prefix":"10.1242","volume":"17","author":[{"given":"Nadia","family":"Alissa","sequence":"first","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Cancer Biology , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Bin","family":"Fang","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Medrano","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Bergeron","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuka","family":"Kozai","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingting","family":"Hu","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Redding","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Thyfault","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 3 Department of Cell Biology and Physiology and Internal Medicine-Division of Endocrinology , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Hamilton-Reeves","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 4 Department of Urology , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Berkland","sequence":"additional","affiliation":[{"name":"University of Kansas 5 Department of Pharmaceutical Chemistry , , Lawrence, KS 66045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-3621","authenticated-orcid":false,"given":"Nikki","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Cancer Biology , , Kansas City, KS 66160 , USA"},{"name":"University of Kansas Medical Center 2 Department of Pathology and Laboratory Medicine , , Kansas City, KS 66160 , USA"},{"name":"University of Kansas Cancer Center 6 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"2024090913413284600_DMM050398C1","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1139\/apnm-2019-0352","article-title":"The effects of high-intensity interval training and saffron aqueous extract supplementation on alterations of body weight and apoptotic indices in skeletal muscle of 4T1 breast cancer-bearing mice with cachexia","volume":"45","author":"Ahmadabadi","year":"2020","journal-title":"Appl. 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