title: Macrophage inhibitory cytokine-1: a review of its pleiotropic actions in cancer.
abstract: OBJECTIVE
  The macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-β (TGF-β) superfamily that can serve as a potential immune-therapeutic target and/or a prognostic biomarker for the treatment of some cancers. This article reviews the current published data on the molecular and clinical application of MIC-1 in cancer.
  
  
  METHODS
  Literature review was conducted using Medline, PubMed, Embase and Cochrane databases.
  
  
  RESULTS
  MIC-1 is the only known secreted p53-regulated cytokine and therefore can serve as a biomarker for p53 activation both in vitro and in vivo. MIC-1 gene can be activated by cyclooxygenase inhibitors and has pro-apoptotic and anti-tumour activities. Although MIC-1 may induce anti-tumour role in the early stages of cancer, it can promote the invasiveness and metastatic behaviour in advanced stages. Greater concentration of MIC-1 was associated with the induction of cancer-related anorexia and weight loss in animals and humans. Of clinical interest, MIC-1 out-performs all available biomarkers including CA19-9 in the differentiation of patients with resectable pancreatic cancer from patients with benign pancreatic disease. MIC-1 gene was over-expressed in colorectal cancer (CRC), and a progressive rise of MIC-1 serum levels was noted in patients with adenomatous polyps and further in patients with CRC.
  
  
  CONCLUSIONS
  MIC-1 cytokine has the potential characteristics for a new diagnostic biomarker and a target for cancer treatment. Further research however is required to characterise MIC-1 receptors and to revalidate its diagnostic power in larger and better-standardised clinical studies.
authors.affiliation: The University of Salford, Manchester, UK.
authors.forename: Yazan S
authors.initials: YS
authors.lastname: Khaled
authors.forename: Eyad
authors.initials: E
authors.lastname: Elkord
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Ammori
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology*; D055436:Growth Differentiation Factor 15 / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology*
chemical_list: D014408:Biomarkers, Tumor; D055436:Growth Differentiation Factor 15