gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Ets-1 dependent expression of transferrin receptors in glioma mediates iron accumulation, reactive oxygen species generation and tumour progression

Ets-1 abhängige Expression von Transferrinrezeptoren in Gliomen vermittelt Eisenakkumulation, ROS-Generation und Tumorprogression

Meeting Abstract

  • corresponding author D. Markovic - Klinik für Neurochirurgie, Helios Klinikum Berlin Buch, Berlin
  • R. Glass - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin, Berlin
  • S. Chirasani - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin, Berlin
  • M. Synowitz - Klinik für Neurochirurgie, Helios Klinikum Berlin Buch, Berlin
  • H. Kettemann - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin, Berlin

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 082

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc337.shtml

Veröffentlicht: 11. April 2007

© 2007 Markovic et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective: Glioblastomas are long known to overexpress transferrin receptors (TfRs), which mediate the cellular uptake of iron. In pathologic brain tissue, iron can accumulate intracellularly and causes deleterious effects, presumably through the generation of reactive oxygen species (ROS) via the Fenton reaction. Tumour cells appear to generate high ROS levels to maintain their malignant potential.

Methods: Measurment of intracellular iron content by iron imaging, ROS levels measuring by using H2DCFDA, manipulating TfR expression by expressing dominant negative form of Ets-1, testing glioma invasiveness in brain slice culture

Results: We show that the transcription factor Ets-1 regulates the expression of TfRs and thereby mediates iron accumulation, ROS generation and tumour progression in human glioblastoma cell lines. Blocking Ets-1 activity by stable transfection of the dominant negative form of Ets-1 (Ets-1Dn) in the human glioblastoma cell line U373 attenuated the expression of transferrin receptors, changed cell morphology, decreased their proliferation, and significantly attenuated the migration of glioma cells. Concentration of free iron (Fe+2), as measured by iron imaging using Phen Green Sk, and ROS levels measured by using H2DCFDA, were both down regulated in U373 Ets-1DN cells compared to wild type U373 cells. Stable overexpression of TfRs in Ets-1Dn cells compensated the effect of blocking Ets-1 activity. The cells had similar levels of free iron, ROS and proliferation as wild-type glioma cells. Moreover, overexpression of TfR by transfection into a human astrocytoma line (1321N1) with low malignancy strongly increased the proliferation of these cells. Ets-1 binding to the TfR promoter region is essential for driving the expression of TfR in human glioma cells as demonstrated by reporter gene activation assays.

Conclusions: The altered expression of transferrin receptors in human glioma cells, regulated by Ets-1, mediates ROS signalling, proliferation and migration and thereby enhances glioma progression.