Die Rolle des Makrophagen-Migrations-Inhibitions-Faktors (MIF) in primären humanen Glioblastomzellen

Das Glioblastoma multiforme (GBM) ist der häufigste und bösartigste primäre Hirntumor und trotz einer multimodalen Therapie aus Resektion, Chemo- und Strahlentherapie beträgt die mittlere Überlebenszeit bei Diagnosestellung eines Glioblastoma multiforme nur 15 Monate. Diese ernüchternde Zahl legt na...

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Bibliographic Details
Main Author: Streiber, Nina
Contributors: Dodel, Richard (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2012
Online Access:PDF Full Text
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Macrophage migration inhibitory factor (MIF) is a protein, which is over-expressed in many tumors, such as colon, melanoma, prostate and also 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 ERK1/2MAPK 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 showed 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 decreases 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.