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

Membrane Hsp70 expression, a histological marker for primary glioblastoma is elevated in patients' serum samples

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
  • 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
  • J.C. Tonn - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • C. Schichor - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München

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.07.11

DOI: 10.3205/12dgnc224, URN: urn:nbn:de:0183-12dgnc2244

Published: June 4, 2012

© 2012 Thorsteinsdottir et al.
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Outline

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Objective: Tumor cells, in contrast to non-neoplastic cells, have the capacity to translocate cytosolic heat shock protein 70 (Hsp70) on their plasma membrane in different cancer types where it can be detected specifically by cmHsp70.1 monoclonal antibody. The biological function of membrane Hsp70 remains unclear, but it stimulates immunomodulatory response by activation of natural killer cells. For the first time, we investigated the expression of membrane Hsp70 in glioblastoma within the tumor heterogenity in cell culture and in tissue and serum samples of patients with different glioma entities.

Methods: In order to clearly define the membrane Hsp70-expressing cell type within a heterogenic tumor cell culture, we performed flow cytometric analysis on different glioma subpopulations (endothelial, mesenchymal, CD133-positive cells, primary culture) and determined membrane Hsp70 secretion by ELISA from the supernatants (n = 3). Membrane Hsp70 expression was analyzed immunohistochemically in glioma with regard to tumor grading, subcellular distribution within glioblastoma tissue (n = 49). Also glioblastoma entity (primary vs. secondary) was distinguished. Furthermore, serum samples of the corresponding patients were analyzed for concentration of membrane Hsp70 (n = 49).

Results: In FACS-analysis, membrane Hsp70 is strongly expressed in primary glioblastoma cell cultures and tumor-initiating CD133-positive cells, but not in other recruited host subpopulations. Supernatant of the cells showed identical membrane Hsp70 secretion profiles of the different cell types. Immunohistochemistry showed that membrane Hsp70 is selectively expressed in primary glioblastoma, but not in low-grade, anaplastic and secondary tumors. The corresponding serum samples of the patients showed that selectively patients with primary glioblastoma had serum concentrations over 2000 pg/ml.

Conclusions: In glioblastoma, we can conclude that this marker serves as tumor-specific target which is restricted to tumor cells. This marker is uniquely expressed in primary glioblastoma and could differentiate the de-novo-origin from secondary glioblastoma. Surprisingly, membrane Hsp70 could also be detected at higher levels in patients with glioblastomas. As molecular markers carry a strong prognostic and predictive value, the biological function of membrane Hsp70 has to be further analyzed in order to tailor the treatment strategy to individual cancer patients regarding their molecular profile.