gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

Transferrin receptor mediated iron accumulation controls proliferation and glutamate release in glioma cells

Meeting Abstract

  • D. Markovic - Neurochirurgie, Helios-Klinikum Berlin Buch
  • G. Rainer - Max Delbrück Zentrum Berlin
  • S. Michael - Neurochirurgie Charité – Universitätsmedizin Berlin
  • C. Sridhar - Max Delbrück Zentrum Berlin
  • K. Jürgen - Neurochirurgie, Helios-Klinikum Berlin Buch
  • K. Helmut - Max Delbrück Zentrum Berlin

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP06-11

DOI: 10.3205/09dgnc315, URN: urn:nbn:de:0183-09dgnc3153

Published: May 20, 2009

© 2009 Markovic et al.
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Outline

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Objective: To determine whether chemical manipulation of intracellular iron influences malignant behavior of glioma cells.

Methods: Proliferation measurements by BrdU test, ROS level measurements using H2DCFDA, Western blotting, immunoprecipitation, in vivo U373 glioma model, immunofluorescence microscopy.

Results: As we demonstrated previously, altered expression of transferrin receptors in human glioma cells regulated by Ets-1 mediates ROS signaling, proliferation, and migration and thereby enhances glioma progression.

We could show that iron- and oxidant-chelators attenuated tumor-proliferation in vitro and tumor-size in vivo and that the TfR-induced oxidant accumulation modified cellular signaling by inactivating a protein tyrosine phosphatase (LMW-PTP), activating MAPK and Akt, and by inactivating p21/cdkn1a and pRB. Inactivation of these cell cycle regulators facilitated S-phase entry. Besides its effect on proliferation, TfR also boosted glutamate release, which caused NMDA receptor-mediated reduction of neuron cell mass.

Conclusions: The reduction of ROS by chemical chelation reduces glioma proliferation and toxic glutamate release.