The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism

Growth Factors. 2011 Oct;29(5):187-95. doi: 10.3109/08977194.2011.607137. Epub 2011 Aug 11.

Abstract

Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is associated with cardiovascular disease, inflammation, body weight regulation and cancer. Its serum levels facilitate the diagnosis and prognosis of cancer and vascular disease. Furthermore, its serum levels are a powerful predictor of all-cause mortality, suggesting a fundamental role in biological processes associated with ageing. In cancer, the data available suggest that MIC-1/GDF15 is antitumorigenic, but this may not always be the case as disease progresses. Cancer promoting effects of MIC-1/GDF15 may be due, in part, to effects on antitumour immunity. This is suggested by the anti-inflammatory and immunosuppressive properties of MIC-1/GDF15 in animal models of atherosclerosis and rheumatoid arthritis. Furthermore, in late-stage cancer, large amounts of MIC-1/GDF15 in the circulation suppress appetite and mediate cancer anorexia/cachexia, which can be reversed by monoclonal antibodies in animals. Available data suggest MIC-1/GDF15 may be an important molecule mediating the interplay between cancer, obesity and chronic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Anorexia / metabolism
  • Anorexia / therapy
  • Biomarkers
  • Cachexia / metabolism
  • Cachexia / therapy
  • Cardiovascular Diseases / metabolism
  • Cell Line, Tumor
  • Disease Progression
  • Growth Differentiation Factor 15 / blood
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Mice
  • Neoplasms / immunology
  • Neoplasms / metabolism*

Substances

  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15