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Isolation of a new cell population in the glioblastoma microenvironment

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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.

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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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Acknowledgments

We thank neurosurgeons (Eric Lioret, CHU, Tours; Phong Dam Hieu, CHU, Brest; Abderrahmane Hamlat, CHU, Rennes) for supplying tumor samples, and the central committee of neuropathologists (Delphine Loussouarn, CHU, Nantes; Stephan Saikali, CHU, Rennes; Sophie Michalak, CHU, Angers; Isabelle Quintin, CHU, Brest). We also thank Emilie Munnier (Service d’Oncologie Médicale, CHRU, Tours), Jérôme Cayon (INSERM U646, Angers), Anne Bordron (Laboratoire de Thérapie Cellulaire, CHU, Brest), Lucie Karayan-Tapon (INSERM U935, Poitiers), Maryvonne Ardourel (Laboratoire de Neurobiologie, Orléans) and Lisa Oliver (INSERM U601, Nantes) for their help in the preparation of cell samples. We thank Pierre Legras and Jérôme Roux (Service Commun d’Animalerie Hospitalo-Universitaire, Angers), Catherine Guillet (Service Commun de Cytométrie et d’Analyse Nucléotidique, Angers), Marina Denyset, and the members of the Cancéropole Grand Ouest for allowing us to use their facilities. This work was supported by the French National Cancer Institute (INCa) and the Ligue Départementale de Lutte Contre le Cancer.

Author information

Authors and Affiliations

  1. LUNAM Université, Ingénierie de la Vectorisation Particulaire, 49933, Angers, France

    Anne Clavreul & Philippe Menei

  2. INSERM, Unit 646, 49933, Angers, France

    Anne Clavreul & Philippe Menei

  3. Département de Neurochirurgie, CHU d’Angers, 4 Rue Larrey, 49933, Angers, France

    Anne Clavreul & Philippe Menei

  4. Plate-forme Génomique Santé Biogenouest®, IFR 140, 35043, Rennes, France

    Amandine Etcheverry & Jean Mosser

  5. CNRS, UMR 6061, Institut Génétique et Développement de Rennes, 35043, Rennes, France

    Amandine Etcheverry, Véronique Quillien & Jean Mosser

  6. Université Rennes 1, UEB, IFR 140, Faculté de Médecine, 35043, Rennes, France

    Amandine Etcheverry, Véronique Quillien & Jean Mosser

  7. Service de Génétique Moléculaire et Génomique, CHU, 35043, Rennes, France

    Amandine Etcheverry & Jean Mosser

  8. Centre Régional de Lutte Contre le Cancer Paul Papin, 49100, Angers, France

    Agnès Chassevent

  9. Centre Eugène Marquis, Département de Biologie, 35042, Rennes, France

    Véronique Quillien & Tony Avril

  10. INSERM U921, 37032, Tours, France

    Marie-Lise Jourdan

  11. Laboratoire de Cancérologie, CHU, 37044, Tours, France

    Marie-Lise Jourdan

  12. Laboratoire Pathologie Cellulaire et Tissulaire, CHU, 49933, Angers, France

    Sophie Michalak

  13. Service de Neurochirurgie, CHU, 37044, Tours, France

    Patrick François

  14. Groupe Gliome Brestois, Service de Biochimie et Biologie Moléculaire, UFR Médecine, CHU, 29238, Brest, France

    Jean-Luc Carré

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  1. Anne Clavreul
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  2. Amandine Etcheverry
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  3. Agnès Chassevent
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  4. Véronique Quillien
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  6. Marie-Lise Jourdan
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  7. Sophie Michalak
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  8. Patrick François
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  9. Jean-Luc Carré
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  10. Jean Mosser
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  11. Philippe Menei
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The Grand Ouest Glioma Project Network

Corresponding author

Correspondence to Philippe Menei.

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Clavreul, A., Etcheverry, A., Chassevent, A. et al. Isolation of a new cell population in the glioblastoma microenvironment. J Neurooncol 106, 493–504 (2012). https://doi.org/10.1007/s11060-011-0701-7

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  • DOI: https://doi.org/10.1007/s11060-011-0701-7

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