{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:45:54Z","timestamp":1788576354750,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cachexia\u2010associated skeletal muscle wasting or \u2018sarcopenia\u2019 is highly prevalent in ovarian cancer and contributes to poor outcome. Drivers of cachexia\u2010associated sarcopenia in ovarian cancer remain elusive, underscoring the need for novel and better models to identify tumour factors inducing sarcopenia. We aimed to assess whether factors present in ascites of sarcopenic vs. non\u2010sarcopenic ovarian cancer patients differentially affect protein metabolism in skeletal muscle cells and to determine if these effects are correlated to cachexia\u2010related patient characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifteen patients with an ovarian mass and ascites underwent extensive physical screening focusing on cachexia\u2010related parameters. Based on computed tomography\u2010based body composition imaging, six cancer patients were classified as sarcopenic and six were not; three patients with a benign condition served as an additional non\u2010sarcopenic control group. Ascites was collected, and concentrations of cachexia\u2010associated factors were assessed by enzyme\u2010linked immunosorbent assay. Subsequently, ascites was used for <jats:italic>in vitro<\/jats:italic> exposure of C2C12 myotubes followed by measurements of protein synthesis and breakdown by radioactive isotope tracing, qPCR\u2010based analysis of atrophy\u2010related gene expression, and NF\u2010\u03baB activity reporter assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>C2C12 protein synthesis was lower after exposure to ascites from sarcopenic patients (sarcopenia 3.1\u00a0\u00b1\u00a00.1\u00a0nmol\/h\/mg protein vs. non\u2010sarcopenia 5.5\u00a0\u00b1\u00a00.2\u00a0nmol\/h\/mg protein, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), and protein breakdown rates tended to be higher (sarcopenia 31.2\u00a0\u00b1\u00a05.2% vs. non\u2010sarcopenia 20.9\u00a0\u00b1\u00a01.9%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.08). Ascites did not affect MuRF1, Atrogin\u20101, or REDD1 expression of C2C12 myotubes, but NF\u2010\u03baB activity was specifically increased in cells exposed to ascites from sarcopenic patients (sarcopenia 2.2\u00a0\u00b1\u00a00.4\u2010fold compared with control vs. non\u2010sarcopenia 1.2\u00a0\u00b1\u00a00.2\u2010fold compared with control, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01). Protein synthesis and breakdown correlated with NF\u2010\u03baB activity (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a0\u22120.60, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03 and <jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a00.67, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01, respectively). The skeletal muscle index of the ascites donors was also correlated to both <jats:italic>in vitro<\/jats:italic> protein synthesis (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a00.70, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.005) and protein breakdown rates (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a0\u22120.57, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ascites of sarcopenic ovarian cancer patients induces pronounced skeletal muscle protein metabolism changes in C2C12 cells that correlate with clinical muscle measures of the patient and that are characteristic of cachexia. The use of ascites offers a new experimental tool to study the impact of both tumour\u2010derived and systemic factors in various cachexia model systems, enabling identification of novel drivers of tissue wasting in ovarian cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12885","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T07:43:36Z","timestamp":1640331816000},"page":"311-324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ovarian cancer ascites induces skeletal muscle wasting <i>in vitro<\/i> and reflects sarcopenia in patients"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-6162","authenticated-orcid":false,"given":"Jorne","family":"Ubachs","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"GROW\u2014School for 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 Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Pasmans","sequence":"additional","affiliation":[{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of Human Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon C.","family":"Langen","sequence":"additional","affiliation":[{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of Pulmonology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth C.R.","family":"Meex","sequence":"additional","affiliation":[{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of Human Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie A.J.H.M.","family":"van Bijnen","sequence":"additional","affiliation":[{"name":"Department of Surgery Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrina","family":"Lambrechts","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"GROW\u2014School for Oncology and Developmental Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toon","family":"Van Gorp","sequence":"additional","affiliation":[{"name":"Department of 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander S.","family":"Rensen","sequence":"additional","affiliation":[{"name":"Department of Surgery Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The 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