title: Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells.
abstract: Macrophage migration inhibitory factor (MIF) is a protein that is overexpressed in many tumors, such as colon and prostate cancer, melanoma, and glioblastoma multiforme (GBM). In its function as a cytokine, MIF induces angiogenesis, promotes cell cycle progression, and inhibits apoptosis. Recently, the molecular signal transduction has been specified: MIF has been found to be a ligand to the CD74/CD44-receptor complex and to activate the ERK1/2 MAPK cascade. In addition MIF binds to the chemokine receptors CXCR2 and CXCR4. This effects an integrin-dependent leukocyte arrest and mediates leukocyte chemotaxis. Recent work has described a clearer role of MIF in GBM tumor cell lines. The current study used human primary GBM cells. We show that inhibition of MIF with ISO-1, an inhibitor of the D-dopachrome tautomerase site of MIF, reduced the growth rate of primary GBM cells in a dose-dependent manner, and in addition ISO-1 increased protein expression of MIF and its receptors CD74, CXCR2, and CXCR4 in vitro but decreased expression of CD44. Furthermore, hypoxia as cell stressor increases the protein expression of MIF in primary GBM cells. These results underscore the importance of MIF in GBM and show that MIF and its receptors may be a promising target for the treatment of malignant gliomas.
authors.affiliation: Department of Neurology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Baron
authors.forename: Oliver
authors.initials: O
authors.lastname: Deuster
authors.forename: Carmen
authors.initials: C
authors.lastname: Noelker
authors.forename: Carsten
authors.initials: C
authors.lastname: Stüer
authors.forename: Herwig
authors.initials: H
authors.lastname: Strik
authors.forename: Carlo
authors.initials: C
authors.lastname: Schaller
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Bacher
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018390:Gene Targeting / Q000379:methods; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D007555:Isoxazoles / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D000970:Antineoplastic Agents; D007555:Isoxazoles; D008263:Macrophage Migration-Inhibitory Factors; D011971:Receptors, Immunologic; C033184:macrophage migration inhibitory factor receptor; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human