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- W2978598231 abstract "Background - The majority of patients with advanced cancer develop cachexia, aweight loss syndrome that severely reduces quality of life and limits survival. Ourunderstanding of the underlying mechanisms that cause the condition is limited, andthere are currently no treatment options that can completely reverse cachexia. Severaltumor-derived factors and inflammatory mediators have been suggested to contributeto weight loss in cachectic patients. However, inconsistencies between studies arerecurrent. Activin A and IL-6 are among the best studied factors that seem to beimportant, and several studies support their individual role in cachexia development.Methods – We investigated the interplay between activin A and IL-6 in the cachexiainducing TOV21G cell line both in culture and in tumours in mice. We previously foundthat the human TOV21G cells secrete IL-6 that induce autophagy in reporter cells andcachexia in mice. Using this established cachexia cell model, we targeted autocrinePowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationactivin A by genetic, chemical and biological approaches. The secretion of IL-6 fromthe cancer cells was determined both in culture and tumor-bearing mice by a speciesspecific ELISA. Autophagy reporter cells were used to monitor the culture medium forautophagy inducing activities and muscle mass changes were evaluated in tumorbearing mice.Results – We show that activin A acts in an autocrine manner to promote the synthesisand secretion of IL-6 from cancer cells. We find that this is important for the ability ofthe cancer cells to accelerate autophagy in non-cancerous cells. Consistently,interfering with activin A signaling in cachectic tumor-bearing mice reduces serumlevels of cancer cell-derived IL-6 and reverses cachexia. Thus, our data support afunctional link between activin and IL-6 signaling pathways, and indicate thatinterference with activin A-induced IL-6 secretion from the tumor has therapeuticpotential for cancer-induced cachexia." @default.
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- W2978598231 date "2019-01-01" @default.
- W2978598231 modified "2023-09-23" @default.
- W2978598231 title "Autocrine activin A signaling in cancer cells controls secretion of IL-6 and autophagy incancer cachexia" @default.
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