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Cortical and Subventricular Zone Glioblastoma-Derived Stem-Like Cells Display Different Molecular Profiles and Differential In Vitro and In Vivo Properties

  • Translational Research and Biomarkers
  • Published:
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Abstract

Background

Cellular self-renewal capacity in glioblastomas is heterogeneous, with only stem-like cells having this property. These cells generate a specific tumor phenotype, but no link with tumor location or molecular characteristics has ever been made.

Methods

Two cells lines, established from cell-dissociated glioblastomas and A2B5+ magnetic cell sorting, were used to decipher the mechanisms of cell migration in glioblastomas. GBM6 was derived from a glioblastoma close to the subventricular zone, whereas GBM9 was derived from a cortical glioblastoma and contained a high number of CD133+ cells.

Results

Orthotopic injections in both the subventricular zone and the cortex of nude mice showed that GBM6 and GBM9 cells had a differential pattern of migration that mirrored that of adult and fetal normal neural stem cells, respectively. GBM6 demonstrated higher tumorigenicity than GBM9, and whichever cell line was injected, subventricular zone-implanted tumors were larger than cortical ones. In vitro, GBM6 and GBM9 displayed high autorenewal and proliferation rates, and their expression profiles and genomic status showed that they had distinctive molecular signatures: GBM6 was classified as a mesenchymal glioblastoma and GBM9 as a proneural glioblastoma.

Conclusions

Altogether, our findings suggest that tumor location in addition to molecular signature influence tumor growth and migration pattern.

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Acknowledgment

This work was supported by grants from the INCA, ARTC-Sud, SFCE, GEFLUC, and the CIT national program. Tumors were collected from the AP-HM tumor bank (2008/70).

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Authors and Affiliations

  1. Inserm U911, Marseille, France

    Aurélie Tchoghandjian PhD, Nathalie Baeza-Kallee PhD, Philippe Metellus PhD, Carole Colin PhD & Dominique Figarella-Branger PhD

  2. Faculté de Médecine la Timone, Aix Marseille Université, Marseille, France

    Aurélie Tchoghandjian PhD, Nathalie Baeza-Kallee PhD, Philippe Metellus PhD, Carole Colin PhD & Dominique Figarella-Branger PhD

  3. CNRS, Marseille, France

    Christophe Beclin PhD & Geneviève Rougon PhD

  4. Institut de Biologie du Développement de Marseille-Luminy, Marseille, France

    Christophe Beclin PhD & Geneviève Rougon PhD

  5. Faculté des Sciences de Luminy, Aix Marseille Université, Marseille, France

    Christophe Beclin PhD & Geneviève Rougon PhD

  6. Service de Neurochirurgie, Hôpital de la Timone, Assistance Publique—Hôpitaux de Marseille, Marseille, France

    Philippe Metellus PhD

  7. Inserm, U842, Lyon, France

    François Ducray PhD

  8. Université Lyon 1, Lyon, France

    François Ducray PhD

  9. Inserm, U599, Marseille, France

    José Adélaïde PhD

  10. Département d’Oncologie Moléculaire, Institut Paoli-Calmettes, Marseille, France

    José Adélaïde PhD

  11. Service d’Anatomie Pathologique et de Neuropathologie, Hôpital de la Timone, Assistance Publique—Hôpitaux de Marseille, Marseille, France

    Dominique Figarella-Branger PhD

Authors
  1. Aurélie Tchoghandjian PhD
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  2. Nathalie Baeza-Kallee PhD
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Corresponding author

Correspondence to Dominique Figarella-Branger PhD.

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Tchoghandjian, A., Baeza-Kallee, N., Beclin, C. et al. Cortical and Subventricular Zone Glioblastoma-Derived Stem-Like Cells Display Different Molecular Profiles and Differential In Vitro and In Vivo Properties. Ann Surg Oncol 19 (Suppl 3), 608–619 (2012). https://doi.org/10.1245/s10434-011-2093-5

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  • DOI: https://doi.org/10.1245/s10434-011-2093-5

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