Artikel
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
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Autoren
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N.O. Schmidt
- Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
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H. Günther
- Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
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H. Meissner
- Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
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F.J. Müller
- Zentrum für Integrative Psychiatrie, Universität Schleswig-Holstein, Campus Kiel
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M. Westphal
- Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
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K. Lamszus
- Klinik und Poliklink für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
| Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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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.
