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Anticancer Res. 2010 Sep;30(9):3301-8.

Maturation of tumor vasculature by interferon-beta disrupts the vascular niche of glioma stem cells.

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1
Department of Surgery, St Jude Children's Research Hospital, University of Tennessee Health Science Center, Memphis, TN 38105-3678, USA.

Abstract

BACKGROUND:

The vascular niche necessary for cancer stem cell maintenance is a potential target for cancer therapy.

MATERIALS AND METHODS:

Human glioma xenografts were treated with IFN-β delivered systemically via a liver-targeted, adeno-associated viral vector. The vascular niche was examined with immunofluorescence for glioma stem cells, endothelial cells, and perivascular cells.

RESULTS:

Although IFN-β was not directly toxic to glioma stem cells in vitro, IFN-β decreased tumor size and the number of stem cells recovered in both heterotopic and orthotopic models. Treatment with IFN-β increased perivascular cells investing the tumor vasculature (6-fold) distancing stem cells from endothelial cells. Additionally, vascular smooth muscle cells co-cultured between stem cells and endothelial cells decreased stem cell recovery.

CONCLUSION:

Continuous delivery of IFN-β decreased the number of stem cells in glioma xenografts by disrupting the vascular niche through an increase in perivascular cells, which created a barrier between the glioma stem cells and the endothelial cells.

PMID:
20944101
[Indexed for MEDLINE]
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