Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells

Nina Baron, Oliver Deuster, Carmen Noelker, Carsten Stüer, Herwig Strik, Carlo Schaller, Richard Dodel, Bernhard Meyer, Michael Bacher

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Pages (from-to)711-717
Number of pages7
JournalJournal of Neuroscience Research
Volume89
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Cell death
  • Cytokine
  • Glioblastoma
  • Macrophage inhibitory factor
  • Neuronal survival

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