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

Williams RF, Sims TL, Tracey L, Myers AL, Ng CY, Poppleton H, Nathwani AC, Davidoff AM.
Source: Anti Cancer Res
Publication Date: (2010)
Issue: 30(9): 3301-8
Research Area:
Cancer Research/Cell Biology
Basic Research
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Species: human
Tissue Origin: vein
SMC, umbilical artery (UASMC) human
Species: human
Tissue Origin: artery
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-ß 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-ß was not directly toxic to glioma stem cells in vitro, IFN-ß decreased tumor size and the number of stem cells recovered in both heterotopic and orthotopic models. Treatment with IFN-ß 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-ß 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.