Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1.
Nat Med
; 13(11): 1333-40, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17982462
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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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Redução de Peso
/
Anorexia
/
Família Multigênica
/
Citocinas
Limite:
Animals
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Humans
/
Male
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article