Tumor and endothelial cell hybrids participate in glioblastoma vasculature.

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.

journal_name

Biomed Res Int

authors

El Hallani S,Colin C,El Houfi Y,Idbaih A,Boisselier B,Marie Y,Ravassard P,Labussière M,Mokhtari K,Thomas JL,Delattre JY,Eichmann A,Sanson M

doi

10.1155/2014/827327

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

827327

eissn

2314-6133

issn

2314-6141

journal_volume

2014

pub_type

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