gms | German Medical Science

62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

07. - 11. Mai 2011, Hamburg

Tumor (stem) cell-derived Tenascin-W is primarily found in the perivascular niche of primary glioblastomas

Meeting Abstract

  • C. Dictus - Division of Neurosurgical Research, Department of Neurosurgery, University Hospital Heidelberg, Germany
  • R. Chiquet-Ehrismann - Friedrich Miescher Institute, Novartis Research Foundation, Basel, Switzerland
  • B. Lahrmann - Institute of Medical Biometry and Informatics, Hamamatsu Tissue Imaging and Analysis (TIGA) Centre, University of Heidelberg, Germany
  • K. Safferling - Institute of Medical Biometry and Informatics, Hamamatsu Tissue Imaging and Analysis (TIGA) Centre, University of Heidelberg, Germany
  • C. Herold-Mende - Division of Neurosurgical Research, Department of Neurosurgery, University Hospital Heidelberg, Germany
  • A. Unterberg - Division of Neurosurgical Research, Department of Neurosurgery, University Hospital Heidelberg, Germany

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.07.12

DOI: 10.3205/11dgnc049, URN: urn:nbn:de:0183-11dgnc0494

Veröffentlicht: 28. April 2011

© 2011 Dictus 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 vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Among the extracellular matrix (ECM) proteins enriched in gliomas, the tenascin family plays an outstanding role in tumorigenesis and neoangiogenesis and, moreover, impacts patient outcome. Recently, Tenascin-W (TN-W) was identified as a novel member of the tenascin family that exhibits a perivascular staining pattern in glioblastoma (GBM) tissue. In this analysis, we sought to determine the source of TN-W expression and its WHO grade-dependent expression pattern in gliomas.

Methods: Tissue sections of normal brain, WHO grade II and III astrocytomas, and secondary and primary GBMs (n=50) were stained immunohistochemically with monoclonal antibodies against human TN-W or the endothelial cell marker CD31. After slide digitalization, the expression was quantified by a Bayes classifier using Visiopharm image analysis software. Additionally, TN-W mRNA and protein levels were determined by LightCycler qPCR and Western Blot in cultures of adult neural progenitor cells (NPCs), different sources of endothelial cells (HUVECs, HMECs and tumor-derived endothelial cells) as well as GBM-derived adherent tumor cells and tumor stem cells (TSCs).

Results: In astrocytomas of all WHO grades, TN-W staining was predominantly localized to the perivascular space even though not every CD31+ blood vessel stained for TN-W. No TN-W staining was detected in normal brain. Most interestingly, TN-W expression was low in WHO grade II and III astrocytomas and secondary GBMs and did not increase concurrently with the WHO-grade dependent rise in CD31+ blood vessels. In contrast, a strong perivascular TN-W expression was found in primary GBMs. Of cellular origin, TN-W mRNA and protein expression were detected primarily in NPC and TSC and to a lesser extent in adherent tumor cell cultures, whereas endothelial cell cultures exhibited only marginal expression levels.

Conclusions: Cellular origin and staining pattern in tumor tissues suggest a contribution of TN-W to the perivascular tumor stem cell niche of primary glioblastoma. Since TN-W is not expressed in normal brain, it might emerge as a promising therapeutic target in primary GBM.