Journal of Neuro-Oncology

, Volume 82, Issue 2, pp 141–150

Expression of VEGFR3 in glioma endothelium correlates with tumor grade

Authors

    • Department of NeurosurgeryKlinikum Großhadern, Ludwig-Maximilians-University Munich
  • F. Trillsch
    • Department of NeurosurgeryKlinikum Großhadern, Ludwig-Maximilians-University Munich
    • Medizinische PoliklinikLudwig-Maximilians-University Munich
  • J. Herms
    • Center for Neuropathology and Prion ResearchLudwig-Maximilians-University Munich
  • N. Thon
    • Department of NeurosurgeryKlinikum Großhadern, Ludwig-Maximilians-University Munich
  • P. J. Nelson
    • Medizinische PoliklinikLudwig-Maximilians-University Munich
  • J. -C. Tonn
    • Department of NeurosurgeryKlinikum Großhadern, Ludwig-Maximilians-University Munich
  • R. Goldbrunner
    • Department of NeurosurgeryKlinikum Großhadern, Ludwig-Maximilians-University Munich
Original Paper

DOI: 10.1007/s11060-006-9272-4

Cite this article as:
Grau, S.J., Trillsch, F., Herms, J. et al. J Neurooncol (2007) 82: 141. doi:10.1007/s11060-006-9272-4

Abstract

Angiogenic processes are regulated by vascular endothelial growth factors (VEGFs) and their receptors VEGFR1 (Flt-1), 2 (Flk-1) and 3 (Flt-4). While VEGFR2 is thought to play a central role in tumor angiogenesis, anti-angiogenic therapies targeting VEGFR2 in glioma models can show escape phenomena with secondary onset of angiogenesis. The purpose of this study was to find explanations for these processes by searching for alternative pathways regulating glioma angiogenesis and reveal a correlation with tumor grade. Thus, VEGFR3, which is not expressed in normal brain, and its ligands VEGF-C and -D, were assessed in high grade (WHO°IV, glioblastomas, GBM) and low grade gliomas [WHO°II astrocytomas (AII)]. In all GBM, a strong protein expression of VEGFR3 was found on tumor endothelium, VEGF-C and -D expression was found on numerous cells in areas of high vascularization. On RNA level, a significant up-regulation of VEGFR3 was detected in GBM compared to AII and non-neoplastic brain. In AII, only very moderate VEGFR3, VEGF-C and -D expression was found on protein and RNA level indicating a correlation of VEGFR3 expression with tumor grade. VEGFR3 signal in both grades was found predominantly on endothelial cells, confirmed by VEGFR3 expression on isolated CD31 positive cells and the expression of various endothelial markers on VEGFR3-positive cells isolated from GBM. The demonstration of a complete angiogenic signaling system that is dependent on tumor grade may influence the traditional paradigm of glioma angiogenesis and may provide a basis for more effective anti-angiogenic treatment strategies.

Keywords

AngiogenesisVascular endothelial growth factor receptorGliomaGlioblastoma lymphangiogenesis

Copyright information

© Springer Science+Business Media, LLC 2006