Journal of Neuro-Oncology

, Volume 106, Issue 3, pp 493–504 | Cite as

Isolation of a new cell population in the glioblastoma microenvironment

  • Anne Clavreul
  • Amandine Etcheverry
  • Agnès Chassevent
  • Véronique Quillien
  • Tony Avril
  • Marie-Lise Jourdan
  • Sophie Michalak
  • Patrick François
  • Jean-Luc Carré
  • Jean Mosser
  • The Grand Ouest Glioma Project Network
  • Philippe Menei
Laboratory Investigation - Human/Animal Tissue

Abstract

Glioblastoma (GB) is a highly infiltrative tumor recurring in 90% of cases within a few centimeters of the resection cavity, even in cases of complete tumor resection and adjuvant chemo/radiotherapy. This observation highlights the importance of understanding this special zone of brain tissue surrounding the tumor. It is becoming clear that the nonneoplastic stromal compartment of most solid cancers plays an active role in tumor proliferation, invasion, and metastasis. Very little information, other than that concerning angiogenesis and immune cells, has been collected for stromal cells from GB. As part of a translational research program, we have isolated a new stromal cell population surrounding GB by computer-guided stereotaxic biopsies and primary culture. We named these cells GB-associated stromal cells (GASCs). GASCs are diploid, do not display the genomic alterations typical of GB cells, and have phenotypic and functional properties in common with the cancer-associated fibroblasts (CAFs) described in the stroma of carcinomas. In particular, GASCs express markers associated with CAFs such as fibroblast surface protein, alpha-smooth muscle actin (α-SMA), and platelet-derived growth factor receptor-beta (PDGFRβ). Furthermore, GASCs have a molecular expression profile different from that of control stromal cells derived from non-GB peripheral brain tissues. GASCs were also found to have tumor-promoting effects on glioma cells in vitro and in vivo. The isolation of GASCs in a tumor of neuroepithelial origin was unexpected, and further studies are required to determine their potential as a target for antiglioma treatment.

Keywords

Translational study Glioblastoma Microenvironment Cancer-associated fibroblasts Primary cultures 

Abbreviations

CAFs

Cancer-associated fibroblasts

DMEM

Dulbecco’s modified Eagle’s medium

FCA

Absolute fold change

GASCs

GB-associated stromal cells

GB

Glioblastoma

HABS

Human AB serum

hMSCs

Human mesenchymal stem cells

IZ

Interface zone

NZ

Necrotic zone

PBZ

Peripheral brain zone

PDGFRβ

Platelet-derived growth factor receptor-beta

Q-PCR

Real-time quantitative polymerase chain reaction

α-SMA

Alpha-smooth muscle actin

TZ

Tumor zone

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Anne Clavreul
    • 1
    • 2
    • 3
  • Amandine Etcheverry
    • 4
    • 5
    • 6
    • 7
  • Agnès Chassevent
    • 8
  • Véronique Quillien
    • 5
    • 6
    • 9
  • Tony Avril
    • 9
  • Marie-Lise Jourdan
    • 10
    • 11
  • Sophie Michalak
    • 12
  • Patrick François
    • 13
  • Jean-Luc Carré
    • 14
  • Jean Mosser
    • 4
    • 5
    • 6
    • 7
  • The Grand Ouest Glioma Project Network
    • 15
  • Philippe Menei
    • 1
    • 2
    • 3
  1. 1.LUNAM Université, Ingénierie de la Vectorisation ParticulaireAngersFrance
  2. 2.INSERMAngersFrance
  3. 3.Département de NeurochirurgieCHU d’AngersAngersFrance
  4. 4.Plate-forme Génomique Santé Biogenouest®, IFR 140RennesFrance
  5. 5.CNRS, UMR 6061, Institut Génétique et Développement de RennesRennesFrance
  6. 6.Université Rennes 1, UEB, IFR 140, Faculté de MédecineRennesFrance
  7. 7.Service de Génétique Moléculaire et GénomiqueCHURennesFrance
  8. 8.Centre Régional de Lutte Contre le Cancer Paul PapinAngersFrance
  9. 9.Centre Eugène Marquis, Département de BiologieRennesFrance
  10. 10.INSERM U921ToursFrance
  11. 11.Laboratoire de CancérologieCHUToursFrance
  12. 12.Laboratoire Pathologie Cellulaire et Tissulaire, CHUAngersFrance
  13. 13.Service de Neurochirurgie, CHUToursFrance
  14. 14.Groupe Gliome BrestoisService de Biochimie et Biologie Moléculaire, UFR Médecine, CHUBrestFrance
  15. 15.Cancéropôle Grand OuestNantesFrance

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