Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1
Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.
|Authors||Johnen, H.;Lin, S.;Kuffner, T.;Brown, D. A.;Tsai, V. W.;Bauskin, A. R.;Wu, L.;Pankhurst, G.;Jiang, L.;Junankar, S.;Hunter, M.;Fairlie, W. D.;Lee, N. J.;Enriquez, R. F.;Baldock, P. A.;Corey, E.;Apple, F. S.;Murakami, M. M.;Lin, E. J.;Wang, C.;During, M. J.;Sainsbury, A.;Herzog, H.;Breit, S. N. :|
|Publisher Name||NATURE MEDICINE|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17982462|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/2220|