gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. bis 14.05.2006, Essen

Paracrine role of glioma-secreted Tenascin-C in tumour-induced angiogenesis

Parakrine Funktion von Gliomzell-sezerniertem Tenascin-C in der Tumor-induzierten Angiogenese

Meeting Abstract

  • corresponding author C. Dictus - Department of Neurosurgery, University of Heidelberg
  • H.H. Steiner - Department of Neurosurgery, University of Heidelberg
  • G. Vasvari - ENT Department, University of Heidelberg
  • A. Unterberg - Department of Neurosurgery, University of Heidelberg
  • C. Herold-Mende - Department of Neurosurgery, University of Heidelberg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 06.89

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Veröffentlicht: 8. Mai 2006

© 2006 Dictus et al.
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Objective: Tenascin-C, an extracellular matrix protein, is predominantly expressed in high grade gliomas but can rarely be found in normal brain. Perivascular expression increases from low grade to high grade gliomas and is significantly correlated with a poor outcome. In general, its function is still unclear. A functional role in tumour-induced angiogenesis has been proposed but has not been investigated in detail so far. Therefore we sought to analyze the paracrine influence of glioblastoma-secreted Tenascin-C on endothelial cells.

Methods: Tenascin-C was quantified in the supernatant of 10 glioblastoma (GBM) short-term cultures with means of an ELISA assay. Then the influence of GBM-secreted Tenascin-C on microvascular endothelial cells (HMEC-1) with respect to proliferation, migration and tubule formation was determined by BrdU-ELISA assay, scrape assay, tube formation in matrigel and by a co-culture system of fibroblasts and human umbilical vein endothelial cells (HUVEC).

Results: Tenascin-C concentration was detected in all GBM cultures in a range from 2 to 791 ng/ml/106 cells. Neutralization of GBM-secreted Tenascin-C with blocking antibodies in increasing doses that are able to detect all splice variants did not alter proliferation on endothelial cells but revealed a significant and dose-dependent decrease in their migration and tubule formation capacity. These results were confirmed in a fibroblast/HUVEC co-culture system, a 2D model that mimics all steps of angiogenesis, where HUVEC presented with a chaotic, disorganized vasculature after an incubation period of 11 days.

Conclusions: Our data indicate that GBM-secreted Tenascin-C plays an important role in the functional organization of tumour-derived vasculature due to its significant influence on migration and tube formation capacity of endothelial cells. Thus future anti-angiogenic therapy of high grade gliomas might also address the pro-angiogenic function of Tenascin-C, e.g. by intravenous or intralesional application of neutralizing antibodies.