gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Membrane bound Hsp70 expression in gliomas: a novel, hypoxia-related marker for progression

Meeting Abstract

  • J. Thorsteinsdottir - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • P. Fu - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • K. Guo - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • M. Gehrmann - Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum Rechts der Isar, Technische Universität München
  • G. Multhoff - Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum Rechts der Isar, Technische Universität München
  • C. Schichor - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMI.05.11

DOI: 10.3205/11dgnc220, URN: urn:nbn:de:0183-11dgnc2207

Published: April 28, 2011

© 2011 Thorsteinsdottir et al.
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Outline

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Objective: Heat-shock-binding-protein 70 (Hsp70) is localized in the cytosol of cells under physiological conditions and regulates folding/unfolding of proteins in order to function as a molecular chaperone to protect cells from lethal damage. In a variety of non-glial tumor entities, Hsp70 is selectively found on the plasma membrane of tumor cells and is considered to be the most stress-inducible member (by hypoxia, chemotherapy and radiation) of the Hsp-family, which induces immune response of natural killer cells. Therefore, we investigated the expression of membrane-bound-Hsp70 in glial tumors and the influence of hypoxia on Hsp70 expression in distinct cell subpopulations, isolated from glioma tissue.

Methods: Membrane bound Hsp70 expression was determined immunohistochemically in glial tumor tissue of different grades. Co-localization of Hsp70-, Glut-1- and HIF-1alpha-expression in primary, secondary and recurrent glioblastoma tissue was shown by immunohistochemistry in consecutive slides. Expression of Hsp70 was determined by FACS-analysis of human glioblastoma cell lines (U87, U251), bone marrow-derived mesenchymal stem cells (bmMSC), glioblastoma cell suspension (PC), isolated mesenchymal stem-like cells (gbMSC) and isolated endothelial cells (gbEC) from glioblastoma. Influence of hypoxia (0.1%) for 72h was investigated on the above-mentioned cell types by FACS-analysis.

Results: Immunohistochemistry showed a grade-dependent Hsp70 expression in glial tumors. Membrane bound Hsp70 - together with hypoxia markers, Glut-1- and HIF-1-alpha are colocalized in perinecrotic regions of consecutive slides, especially in primary and recurrent glioblastoma. In FACS-analysis, Hsp70 is strongly expressed in immortalized glioma cell lines as well as primary glioblastoma cell cultures, weakly in gbMSC, gbEC and bmMSC and intermediately in CD133-positive cells, derived from glioblastoma. Increased Hsp70 expression could be induced by hypoxia in glioblastoma cell lines and primary cultures, but not in gbMSC, gbEC and bmMSC.

Conclusions: For the first time, we describe a grade-dependent expression of membrane bound Hsp70 in gliomas. Hsp70 is predominantly expressed by glioblastoma cells and CD133-positive cells and weakly expressed by recruited subpopulations, like gbMSC, gbEC and bmMSC. Furthermore, induction of Hsp70 seems to be upregulated by hypoxia which is of biological importance. As a consequence, membrane bound Hsp70 could serve as a selective, grade dependent and tumor cell specific protein.