gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

Human glioblastomas contain stem cell-like tumour cells: establishment and characterization of stable tumour stem cell lines as a new tool for studying glioma biology

Menschliche Glioblastome enthalten Stammzell-ähnliche Tumorzellen: Etablierung und Charakterisierung stabiler Tumor-Stammzellinien

Meeting Abstract

  • corresponding author N.O. Schmidt - Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
  • H. Günther - Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
  • H. Meissner - Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
  • F.J. Müller - Zentrum für Integrative Psychiatrie, Universität Schleswig-Holstein, Campus Kiel
  • M. Westphal - Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
  • K. Lamszus - Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg

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. DocSO.03.06

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc178.shtml

Published: May 8, 2006

© 2006 Schmidt 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

Text

Objective: Previous reports have demonstrated that a variety of human tumour entities contain a small subpopulation of cells which display a stem-cell like phenotype and seem to be responsible for driving tumour formation. Here, we describe the establishment and characterization of stable tumour stem cell lines isolated from human glioblastomas.

Methods: Human glioblastoma sphere cultures were established from fresh surgical specimen and propagated using serum-free culture conditions with a variety of growth factors known to support the survival of stem cells. Long-term cultures of tumour-derived neurospheres were extensively characterized using immunohistochemistry, RT-PCR, FACS analysis and differentiation- and self-renewal assays. Tumourigenicity and in vivo growth characteristics were analyzed after intracerebral implantation in nude mice.

Results: We were able to establish nine stable long-term cultures of tumor-stem cells derived from human glioblastomas. Almost 95% of these cells displayed simultaneous expression of the astroglial marker GFAP and various stem cell markers e.g. such as nestin, CD133, sox2, oct4 and bmi1 in the absence of mature neuronal and oligodendroglial markers confirming their relatively uncommited stage. However, under differentiating culture conditions neuronal and oligodendroglial differentiation was observed. Exposure to standard chemotherapeutics in a survival assay in vitro revealed their relative chemoresistance in comparison to tumour cells which do not display stem-cell like features. In contrast to conventional intracerebral glioblastoma xenograft models the intracerebral injection of tumour-stem cells resulted in highly invasive gliomas closely reflecting the growth pattern of tumours seen in patients.

Conclusions: Human glioblastoma derived tumour-stem cells are a subpopulation of tumor cells with distinct biological features much more reflecting the overall heterogenic behaviour of glioblastomas. Tumour-stem cells provide a powerful tool for the investigation of the tumorigenic process and to develop specifically tailored therapeutic approaches.