Author: ["Heiko Johnen","Shu Lin","Tamara Kuffner","David A Brown","Vicky Wang-Wei Tsai","Asne R Bauskin","Liyun Wu","Greg Pankhurst","Lele Jiang","Simon Junankar","Mark Hunter","W Douglas Fairlie","Nicola J Lee","Ronaldo F Enriquez","Paul A Baldock","Eva Corey","Fred S Apple","MaryAnn M Murakami","En-Ju Lin","Chuansong Wang","Matthew J During","Amanda Sainsbury","Herbert Herzog","Samuel N Breit"]
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Abstract
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-β 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.Cite this article
Johnen, H., Lin, S., Kuffner, T. et al. Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1. Nat Med 13, 1333–1340 (2007). https://doi.org/10.1038/nm1677 