title: 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.affiliation: Centre for Immunology, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia.
authors.forename: Heiko
authors.initials: H
authors.lastname: Johnen
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.forename: Tamara
authors.initials: T
authors.lastname: Kuffner
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Vicky Wang-Wei
authors.initials: VW
authors.lastname: Tsai
authors.forename: Asne R
authors.initials: AR
authors.lastname: Bauskin
authors.forename: Liyun
authors.initials: L
authors.lastname: Wu
authors.forename: Greg
authors.initials: G
authors.lastname: Pankhurst
authors.forename: Lele
authors.initials: L
authors.lastname: Jiang
authors.forename: Simon
authors.initials: S
authors.lastname: Junankar
authors.forename: Mark
authors.initials: M
authors.lastname: Hunter
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Fairlie
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Lee
authors.forename: Ronaldo F
authors.initials: RF
authors.lastname: Enriquez
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.forename: Eva
authors.initials: E
authors.lastname: Corey
authors.forename: Fred S
authors.initials: FS
authors.lastname: Apple
authors.forename: Maryann M
authors.initials: MM
authors.lastname: Murakami
authors.forename: En-Ju
authors.initials: EJ
authors.lastname: Lin
authors.forename: Chuansong
authors.initials: C
authors.lastname: Wang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: During
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D000906:Antibodies / Q000008:administration & dosage / Q000502:physiology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D005810:Multigene Family / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015431:Weight Loss / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D016212:Transforming Growth Factor beta