gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Hypoxia-driven erythropoietin-crosstalk between bone marrow derived mesenchymal progenitor cells and malignant gliomas

Meeting Abstract

  • Florian Faber - Tumor-biologisches Labor, Neurochirurgische Klinik, Ludwig-Maximilians-Universität, Klinikum Großhadern, München, Germany
  • Valerie Albrecht - Tumor-biologisches Labor, Neurochirurgische Klinik, Ludwig-Maximilians-Universität, Klinikum Großhadern, München, Germany
  • Ketai Guo - Tumor-biologisches Labor, Neurochirurgische Klinik, Ludwig-Maximilians-Universität, Klinikum Großhadern, München, Germany
  • Kathrin Juerchott - Abteilung für Biochemie und Systembiologie, Universität Potsdam, Potsdam-Golm, Germany
  • Jörg-Christian Tonn - Tumor-biologisches Labor, Neurochirurgische Klinik, Ludwig-Maximilians-Universität, Klinikum Großhadern, München, Germany
  • Christian Schichor - Tumor-biologisches Labor, Neurochirurgische Klinik, Ludwig-Maximilians-Universität, Klinikum Großhadern, München, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1721

DOI: 10.3205/10dgnc192, URN: urn:nbn:de:0183-10dgnc1928

Published: September 16, 2010

© 2010 Faber et al.
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Outline

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Objective: Enhanced proliferation, metabolic stress, necrosis and hypoxia are hallmarks of malignant gliomas. Tumor cells produce a broad variety of factors in order to escape cell death through the loss of oxygenation, such as hypoxia-inducible factor 1 alpha (HIF1 α) and erythropoietin (EPO) / erythropoietin receptor (EPO-R). Moreover, emerging data suggest that bone marrow derived progenitor cells such as mesenchymal stem cells (MSC) may contribute to tumorigenesis in glioblastoma. The aim of the study was to study hypoxia-driven interaction of glioma cells and mesenchymal stems via the EPO / EPO-R axis.

Methods: We analyzed differential EPO and EPO-R expression based on publicly available data sets from whole genome micorarrays and performed consecutive immunohistochemical studies of HIF-1α and EPO-R in 10 glioblastoma samples simultaneously. The expression of the erythropoietin receptor and its ligand erythropoietin were investigated in mesenchymal stem cells and endothelial cells (ECs) isolated from glioblastoma, as well as in bone marrow derived mesenchymal stem cells and glioma cell lines under normoxic and hypoxic conditions by RT-PCR. Furthermore, we characterized their EPO-induced migratory behavior.

Results: The analyses of the high throughput microarray data showed a very low EPO expression, but indicated an expression of EPO-R in glioblastomas and MSCs. HIF-1α as a marker for hypoxia and EPO-R were frequently co-expressed in the surrounding necrotic areas in glioblastoma samples. EPO and EPOR expression was detected heterogeneously and increased under hypoxic conditions in glioma cell lines, but was particularly found in tumor and bone marrow derived MSCs as well as ECs. Erythropoietin showed a pro-migratory effect on tumor isolated MSCs as well as on bone marrow derived MSCs. In addition, the hypoxia-induced up-regulation of EPOR was conducive to the migration toward the EPO-gradient.

Conclusions: Hypoxia-inducible expression of EPO and EPOR is not only limited to glioma cells but mainly up-regulated in MSCs isolated from glioblastomas and their precursor cells from bone marrow. For the first time, we describe that EPO is an essential hypoxia-related stem cell recruitment factor in gliomas. These data support the hypothesis that gliomas use physiological pathways related to hypoxic conditions in order to recruit mesenchymal progenitor cells.