title: Macrophage migration inhibitory factor involvement in breast cancer (Review).
abstract: Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine involved in many cellular processes and in particular carcinogenesis. Here, we review the experimental and clinical published data on MIF and its pathways in breast cancer. Experimental data show that MIF is overexpressed in breast cancer cells (BCC) due, at least partly, to its stabilization by HSP90 and upregulation by HIF-1α. MIF interacts with its main receptor CD74 and its co-receptor CXCR-4, both overexpressed, promoting cell survival by PI3K/Akt activation, a possible link with EGFR and HER2 pathways and inhibition of autophagy. Besides these auto- and paracrine effects on BCC, MIF interacts with BCC microenvironment by several mechanisms: immunomodulation by increasing the prevalence of immune suppressive cells, neo-angiogenesis by its link to HIF-1, and finally BCC transendothelial migration. Clinical studies show higher levels of MIF in breast cancer patients serum compared to healthy volunteers but without obvious clinical significance. In breast cancer tissue, MIF and CD74 are overexpressed in the cancer cells and in the stroma but correlations with classical prognostic factors or survival are elusive. However, an inverse correlation with the tumor size for stromal MIF and a positive correlation with the triple receptor negative tumor status for stromal CD74 seem to be showed. This set of experimental and clinical data shows the involvement of MIF pathways in breast carcinogenesis. Several anti-MIF targeted strategies are being explored in therapeutic goals and should merit further investigations.
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Kindt
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Saussez
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis* / Q000235:genetics; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019746:Intramolecular Oxidoreductases; D008263:Macrophage Migration-Inhibitory Factors; D012799:Sialyltransferases; C497442:HIF1A protein, human; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; C515598:MIF protein, human