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  • Original Article
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Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria

Oncogene volume 27, pages 2897–2909 (2008)Cite this article

Abstract

Tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We generated cell lines from glioblastoma specimens with the goal to obtain model systems for glioma stem cell biology. Unsupervised analysis of the expression profiles of nine cell lines established under neural stem cell conditions yielded two distinct clusters. Four cell lines were characterized by the expression of neurodevelopmental genes. They showed a multipotent differentiation profile along neuronal, astroglial and oligodendroglial lineages, grew spherically in vitro, expressed CD133 and formed highly invasive tumors in vivo. The other five cell lines shared expression signatures enriched for extracellular matrix-related genes, had a more restricted differentiation capacity, contained no or fewer CD133+ cells, grew semiadherent or adherent in vitro and displayed reduced tumorigenicity and invasion in vivo. Our findings show that stable, multipotent glioblastoma cell lines with a full stem-like phenotype express neurodevelopmental genes as a distinctive feature, which may offer therapeutic targeting opportunities. The generation of another distinct cluster of cell lines showing similarly homogeneous profiling but restricted stem cell properties suggests that different phenotypes exist, each of which may lead to the typical appearance of glioblastoma.

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Acknowledgements

We thank Professor Dr Christian Hagel for access to neuropathological information and to viewing tumor slides. We also thank Regina Fillbrandt, Svenja Zapf and Dorothea Zirkel for expert technical assistance and Steve Guerrero and Pete Haverty for their advice and assistance in analysis of SNP chip data. KL and MW are supported by the Deutsche Forschungsgemeinschaft (LA1300/3-1) and by the Erich und Gertrud Roggenbuck-Stiftung. HG is supported by a scholarship of the FAZIT-Stiftung. Material funds were generously provided by the Rudolf-Bartling-Stiftung and the Georg and Jürgen Rickertsen Stiftung.

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Author notes

  1. H S Günther and N O Schmidt: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    H S Günther, N O Schmidt, H Meissner, M Westphal & K Lamszus

  2. Department of Tumor Biology and Angiogenesis, Genentech Inc., South San Francisco, CA, USA

    H S Phillips & S Kharbanda

  3. Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    D Kemming

  4. Department of Molecular Biology, Genentech Inc., South San Francisco, CA, USA

    R Soriano & Z Modrusan

Authors
  1. H S Günther
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  2. N O Schmidt
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Correspondence to K Lamszus.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Günther, H., Schmidt, N., Phillips, H. et al. Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene 27, 2897–2909 (2008). https://doi.org/10.1038/sj.onc.1210949

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