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

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: 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
• Journal: Nature medicine (Nat Med) Vol. 13 Issue 11 Pg. 1333-40 (Nov 2007) ISSN: 1078-8956 [Print] United States
• PMID: 17982462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Cytokines
• GDF15 protein, human
• Gdf15 protein, mouse
• Growth Differentiation Factor 15
• Transforming Growth Factor beta

Topics

• Animals
• Anorexia (genetics, immunology, metabolism, physiopathology)
• Antibodies (administration & dosage, physiology)
• Cell Line, Tumor
• Cytokines (blood, genetics, immunology, physiology)
• Growth Differentiation Factor 15
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Mice, Transgenic
• Multigene Family (immunology)
• Prostatic Neoplasms (blood, immunology, metabolism, physiopathology)
• Transforming Growth Factor beta (genetics, immunology, physiology)
• Weight Loss (genetics, immunology)