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

Activation of Dll4-Notch signalling in primary glioblastoma multiforme

Meeting Abstract

  • N.E. Hindy - Abteilung für Neurochirurgie, Universitätsklinikum Duisburg-Essen
  • N. Lambertz - Abteilung für Neurochirurgie, Universitätsklinikum Duisburg-Essen
  • K. Keyvani - Abteilung für Neuropathologie, Universitätsklinikum Duisburg-Essen
  • I.E. Sandalcioglu - Abteilung für Neurochirurgie, Universitätsklinikum Duisburg-Essen
  • U. Sure - Abteilung für Neurochirurgie, Universitätsklinikum Duisburg-Essen
  • Y. Zhu - Abteilung für Neurochirurgie, Universitätsklinikum Duisburg-Essen

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.01.02

DOI: 10.3205/12dgnc166, URN: urn:nbn:de:0183-12dgnc1663

Published: June 4, 2012

© 2012 Hindy et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor, characterized by massive neovascularisation, necrosis and intense therapy resistance. Deregulated Notch signalling has been implicated in the formation and progression of different malignancies.

Methods: Patients with primary GBM (n = 26) were enrolled for real-time RT-PCR detection of Dll4, Jagged1, Notch1, Notch4 and Hey1. The surgical specimens of patients who underwent anterior temporal lobe resection due to temporal lobe epilepsy served as control (n = 11). Western Blot and immunostaining were performed to confirm the protein level of these components and to reveal the cellular localization of the immunoreactivity, respectively.

Results: The mRNA expression of Dll4, Jagged1, Notch1, Notch4 and Hey1 was significantly upregulated with mean fold expression of 3.12, 3.58, 3.37, 5.77 and 4.89 for Dll4, Jagged1, Notch1, Notch4, and Hey1, respectively. The upregulation of Dll4 and Notch1 was confirmed by Western blot. Immunostaining revealed the immunoreactivity for Dll4 and Notch1 in endothelial cells, tumor cells and microglia/macrophage. Moreover, activation status of Dll4-Notch signalling was positively associated with bizarre vascular pattern, microvascular density, tumor oedema and MGMT promoter methylation.

Conclusions: Activation of Dll4-Notch signalling is implicated in the majority of GBM and associated with clinical features. Targeting Dll4-Notch signalling may be a new therapeutic strategy for a subset of primary human GBM with hyper-activated Notch signalling.