Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1 Academic Article uri icon

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.

authors

  • Johnen, Heiko
  • Lin, Shu
  • Kuffner, Tamara
  • Brown, David A
  • Tsai, Vicky Wang-Wei
  • Bauskin, Asne R
  • Wu, Liyun
  • Pankhurst, Greg
  • Jiang, Lele
  • Junankar, Simon
  • Hunter, Mark
  • Fairlie, W Douglas
  • Lee, Nicola J
  • Enriquez, Ronaldo F
  • Baldock, Paul A
  • Corey, Eva
  • Apple, Fred S
  • Murakami, MaryAnn M
  • Lin, En-Ju
  • Wang, Chuansong
  • During, Matthew J
  • Sainsbury, Amanda
  • Herzog, Herbert
  • Breit, Samuel N

publication date

  • November 2007