{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:18:25Z","timestamp":1790738305159,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Research Council of Norway","award":["139610\/300"],"award-info":[{"award-number":["139610\/300"]}]},{"name":"The Research Council of Norway","award":["223255\/F50"],"award-info":[{"award-number":["223255\/F50"]}]},{"name":"The Norwegian Cancer Society"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The majority of patients with advanced cancer develop cachexia, a weight loss syndrome that severely reduces quality of life and limits survival. Our understanding of the underlying mechanisms that cause the condition is limited, and there are currently no treatment options that can completely reverse cachexia. Several tumour\u2010derived factors and inflammatory mediators have been suggested to contribute to weight loss in cachectic patients. However, inconsistencies between studies are recurrent. Activin A and interleukin 6 (IL\u20106) are among the best studied factors that seem to be important, and several studies support their individual role in cachexia development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the interplay between activin A and IL\u20106 in the cachexia\u2010inducing TOV21G cell line, both in culture and in tumours in mice. We previously found that the human TOV21G cells secrete IL\u20106 that induces autophagy in reporter cells and cachexia in mice. Using this established cachexia cell model, we targeted autocrine activin A by genetic, chemical, and biological approaches. The secretion of IL\u20106 from the cancer cells was determined in both culture and tumour\u2010bearing mice by a species\u2010specific ELISA. Autophagy reporter cells were used to monitor the culture medium for autophagy\u2010inducing activities, and muscle mass changes were evaluated in tumour\u2010bearing mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that activin A acts in an autocrine manner to promote the synthesis and secretion of IL\u20106 from cancer cells. By inhibiting activin A signalling, the production of IL\u20106 from the cancer cells is reduced by 40\u201350% (up to 42% reduction on protein level, <jats:italic>P<\/jats:italic> = 0.0048, and 48% reduction on mRNA level, <jats:italic>P<\/jats:italic> = 0.0308). Significantly reduced IL\u20106 secretion (<jats:italic>P<\/jats:italic> &lt; 0.05) from the cancer cells is consistently observed when using biological, chemical, and genetic approaches to interfere with the autocrine activin A loop. Inhibiting activin signalling also reduces the ability of the cancer cells to accelerate autophagy in non\u2010cancerous cells (up to 43% reduced autophagy flux, <jats:italic>P<\/jats:italic> = 0.0006). Coherent to the <jats:italic>in vitro<\/jats:italic> data, the use of an anti\u2010activin receptor 2 antibody in cachectic tumour\u2010bearing mice reduces serum levels of cancer cell\u2010derived IL\u20106 by 62% (from 417 to 159 pg\/mL, <jats:italic>P<\/jats:italic> = 0.03), and, importantly, it reverses cachexia and counteracts loss of all measured muscle groups (<jats:italic>P<\/jats:italic> &lt; 0.0005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data support a functional link between activin A and IL\u20106 signalling pathways and indicate that interference with activin A\u2010induced IL\u20106 secretion from the tumour has therapeutic potential for cancer\u2010induced cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12489","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T04:50:04Z","timestamp":1566449404000},"page":"195-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Autocrine activin A signalling in ovarian cancer cells regulates secretion of interleukin 6, autophagy, and cachexia"],"prefix":"10.1002","volume":"11","author":[{"given":"Kristine","family":"Pettersen","sequence":"first","affiliation":[{"name":"Department of Biomedical Laboratory Science, Faculty of Natural Sciences NTNU\u2010Norwegian University of Science and Technology  Trondheim Norway"},{"name":"Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine NTNU\u2010Norwegian University of Science and Technology  Trondheim 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