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. 2007 Nov;13(11):1333-40.
doi: 10.1038/nm1677. Epub 2007 Nov 4.

Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1

Heiko Johnen  1 , 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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Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1

Heiko Johnen et al. Nat Med. 2007 Nov.

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-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.

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