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Biomed Res Int. 2014;2014:827327. doi: 10.1155/2014/827327. Epub 2014 Apr 24.

Tumor and endothelial cell hybrids participate in glioblastoma vasculature.

Author information

1
Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
2
UMR911-CRO2, Faculté de Médecine de la Timone, Université de la Méditerranée, 13000 Marseille, France.
3
Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France ; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, 75013 Paris, France.
4
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neuropathologie Raymond Escourolle, 75013 Paris, France.
5
INSERM U833, Collège de France, 75005 Paris, France.

Abstract

BACKGROUND:

Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM). Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM.

MATERIALS AND METHODS:

We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact.

RESULTS:

In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF). By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation.

CONCLUSION:

A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance.

PMID:
24868550
PMCID:
PMC4017715
DOI:
10.1155/2014/827327
[Indexed for MEDLINE]
Free PMC Article

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