gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

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The melanin-concentrating hormone receptor-1 (MCHR1) is overexpressed in glioblastoma and induced by metabolic stress in glioma stem-like cells

Meeting Abstract

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  • A. Schulte - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
  • A. Kathagen - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
  • S. Zapf - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
  • H. Meissner - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
  • M. Westphal - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
  • K. Lamszus - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocFR.07.05

doi: 10.3205/12dgnc218, urn:nbn:de:0183-12dgnc2183

Published: June 4, 2012

© 2012 Schulte et al.
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Outline

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Objective: The current study aimed to identify hypoxia-regulated genes in glioma stem-like cell lines that account for the plasticity of these cells, facilitating adaptation to the tumor microenvironment, specifically the hypoxic niche.

Methods: Glioma stem-like cell lines were established from four different tumors under either normoxic (21% O2, GSN-lines) or hypoxic (1% O2, GSH-lines) conditions, and expression profiles were analyzed by microarrays to identify genes induced by long- versus short-term hypoxia. Of the genes identified, MCHR1 was validated as a specific, hypoxia-inducible target in primary glioma tissue by immunohistochemistry and in glioma stem-like cell cultures at the mRNA level by quantitative RealTime-PCR and at the protein level by FACS analysis and Western blot.

Results: Microarray analysis of glioma stem-like cells, either generated under hypoxic conditions or acutely exposed to 1%O2 (48 h) as a model for adaptation to microenvironmental changes, allowed us to identify a number of genes which are induced or downregulated by either chronic or acute hypoxia. Among the genes inducible by hypoxia, the melanin-concentrating hormone receptor-1 (MCHR1) could be correlated with negative outcome in glioma patients. Analysis of primary GBM tissue as well as of GS-cell-xenografts showed enhanced expression of MCHR1 protein in comparison to normal brain tissue. In glioma stem-like cells, MCHR1 was detected at the mRNA level as well as at the protein level, whereas it was absent in conventional glioma cell lines, grown in the presence of serum. Exposure of GS-cells to hypoxia led to an induction of MCHR1 mRNA and protein, rendering the cells highly responsive to stimulation via MCH.

Conclusions: Glioma stem-like cell cultures and xenografts tumors are a convenient, reproducible model system for the identification of novel hypoxia-induced target genes. The identification of MCHR1 as overexpressed in GBM and as regulated by hypoxia in cell culture points towards an unexpected novel role for this hormone receptor in glioma biology.