Macrophage Inhibitory Cytokine-1: A review of its pleiotropic actions in cancer

Article type: Review Article

Authors: Khaled, Yazan S.^{a; b; c; d} | Elkord, Eyad^{a; b; e} | Ammori, Basil J.^{a; b; c; d; *}

Affiliations: [a] The University of Salford, Manchester, UK | [b] The University of Manchester, Manchester, UK | [c] Department of Upper Gastrointestinal Surgery, Salford Royal Foundation Trust, Manchester, UK | [d] Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK | [e] United Arab Emirates University, Al Ain, United Arab Emirates

Correspondence: [*] Corresponding author: Basil J. Ammori, Consultant Surgeon, Salford Royal Hospital, Stott Lane, Salford, Manchester, M6 8HD, UK. Tel.: +44 161 206 0449; Fax: +44 161 720 2228; E-mail: [email protected].

Abstract: Background and aims: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.

Keywords: Macrophage Inhibitory Cytokine -1, pleiotropic, pancreatic, colorectal, cancer

DOI: 10.3233/CBM-2012-00287

Journal: Cancer Biomarkers, vol. 11, no. 5, pp. 183-190, 2012