MIC-1/GDF15 research from Breit Group
MIC-1/GDF15 is a cytokine and divergent member of the TGF-b superfamily first cloned and characterised by this Group. Its expression is markedly increased in most cells and tissues in response to injury, inflammation or malignancy. As a result, it is frequently overexpressed in many patients with cancer such as those of prostate, breast, colon and pancreas. This overexpression starts early in cancer and can be detected by change in its serum levels. At least early in the course of cancer MIC-1 GDF15 probably helps to limit and control cancer growth and spread. MIC-1/GDF15 expression increases broadly in proportion to the stage and extent of disease and in advancer cancer very high serum levels can lead to anorexia/cachexia, which is mediated by direct actions of this cytokine on appetite regulatory centres in the brain.

Whilst studied less extensively, MIC-1/GDF15 also plays a role in chronic inflammatory processes of diseases such as rheumatoid arthritis and cardiovascular disease. MIC-1/GDF15 is expressed at sites of injury and inflammation such as atherosclerotic vessel wall and rheumatoid arthritis joint. This is reflected by changes in its serum levels, which tend to predict disease course or treatment outcome. Because of disease associated changes is serum levels of MIC-1/GDF15, these levels are a powerful predictor of all cause mortality.

Current MIC-1/GDF15 Research Projects

• The role of MIC-1/GDF15 in the biology of cancer
• The mechanism of action of MIC-1/GDF15 in appetite regulation
• The role of MIC-1/GDF15 in chronic inflammatory diseases

Selected MIC-1/GDF15 Publications

• Bootcov MR^#, Bauskin A^#, Valenzuela SM, Moore AG, Bansal M, He C, Zhang HP, Donnellan M, Mahler S, Pryor K, Walsh B, Nicholson R, Fairlie DF, Por SB, Robbins JM,  Breit SN. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-ß superfamily cluster.  Proc Natl Acad Sci USA.1997:94:11514-11519.
• David A Brown^#, Samuel N Breit^#, Julie Buring, W Douglas Fairlie, Asne R Bauskin and Paul M Ridker. Concentration in plasma of macrophage inhibitory cytokine-1 and the risk of cardiovascular events in women. Lancet. 2002;359:2159-63.
• David A. Brown, Robyn L. Ward, Philip Buckhaults, Tao Liu,  Katharine E. Romans, Nicholas J. Hawkins, Asne R. Bauskin,  Kenneth W. Kinzler, Bert Vogelstein, Samuel N. Breit. MIC-1 serum level and genotype: Associations with progress and prognosis of colorectal carcinoma. Clinical Cancer Research. 2003.9:2642-2650.
• Tao Liu , Asne R. Bauskin, John Zaunders, David A. Brown, Susan Pankhurst, Pamela J. Russell, Samuel N. Brei^t. Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Research. 2003. 63: 5034-5040.
• AR Bauskin, DA Brown, S Junankar, KK Rasiah, S Eggleton, M Hunter, T Liu, D Smith, T Kuffner, G J Pankhurst^, H Johnen, PJ Russell, PD Stricker, JJ Grygiel, JG Kench^, SM Henshall, RL Sutherland, SN Breit. The propeptide mediates formation of stromal stores of proMIC-1: Role in determining prostate cancer outcome. Cancer Res. 2005. 65:2330-6.
• Katri S. Selander^#, David A. Brown^#, Mark Hunter, Renee Desmond, Guillermo Blanco-Sequeiros, Teija Parpala, Juha Risteli, Samuel N. Breit^#, Arja Jukkola-Vuorinen^#. Serum Macrophage Inhibitory Cytokine-1 Concentrations Correlate With The Presence of Prostate Cancer Bone. Cancer Epidemiology, Biomarkers & Prevention. 2007. 6:532-7.
• Brown David A, John Moore, Heiko Johnen, Tom J. Smeets, W., Asne R. Bauskin, Tamara Kuffner, Helen Weedon, Samuel T. Milliken, Paul P. Tak, Malcolm D. Smith, Samuel N. Breit. Serum MIC-1 in rheumatoid arthritis: a potential marker of erosive joint destruction. Arth. Rheum. 2007. 56:753-764.
• Heiko Johnen^#, Shu Lin^#, Tamara Kuffner^#, David A Brown, Vicky Wang-Wei Tsai, Asne R Bauskin, Liyun Wu Greg Pankhurst, Simon Junankar, Mark Hunter, W Douglas Fairlie, Nicola J Lee, Ronald Enriquez, Paul A Baldock, Lele Jiang, Eva Corey, Fred S Apple, MaryAnn M Murakami,  En-Ju Lin, Chuansong Wang, Matthew J During, Amanda Sainsbury, Herbert Herzog^#, Samuel N Breit^#. Tumour-induced anorexia/cachexia is mediated by the TGF-b superfamily cytokine MIC-1. Nature Medicine. 2007. 13:1333-40.
• Brown DA, Lindmark F, Stattin P, Bälter K, Adami HO, Zheng SL, Xu J, Isaacs WB, Grönberg H, ^#Breit SN, and  ^#Wiklund FE. Macrophage Inhibitory Cytokine 1: A New Prognostic Marker in Prostate Cancer. Clin Cancer Res. 2009 15:6658-64.
• Asne R Bauskin, Lele Jiang, X. Wei Luo, Liyun Wu, David A Brown and Samuel N Breit. The TGF-β superfamily cytokine MIC-1/GDF15: Secretory mechanisms facilitate creation of latent stromal stores. J Interferon Cytokine Res. 2010. 30:389-97.
• Fredrik E Wiklund^#, Anna M Bennet^#, Patrik KE Magnusson, Ulrika K Eriksson, Fredrik Lindmark, Liyun Wu, Nasreen Yaghoutyfam, Christopher P Marquis, Pär Stattin, Nancy L Pedersen, Hans-Olov Adami, Henrik Grönberg, Samuel N Breit^#, David A Brown^#. Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality. Aging Cell. 2010. 9:1057-64.

^#Contributed equally

PubMed publications for Professor Breit