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Maturation of Tumor Vasculature by Interferon-beta Disrupts the Vascular Niche of Glioma Stem Cells

Williams, RF; Sims, TL; Tracey, L; Myers, AL; Ng, CYC; Poppleton, H; Nathwani, AC; (2010) Maturation of Tumor Vasculature by Interferon-beta Disrupts the Vascular Niche of Glioma Stem Cells. ANTICANCER RES , 30 (9) 3301 - 3308.

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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-beta delivered systemically via a liver-targeted, adeno-associated viral vector. The vascular niche was examined with immunofluorescence for glioma stern cells, endothelial cells, and perivascular cells. Results: Although IFN-beta was not directly toxic to glioma stem cells in vitro, IFN-beta decreased tumor size and the number of stem cells recovered in both heterotopic and orthotopic models. Treatment with IFN-beta 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-beta 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.

Type: Article
Title: Maturation of Tumor Vasculature by Interferon-beta Disrupts the Vascular Niche of Glioma Stem Cells
Keywords: Glioma, stem cells, interferon-beta, stem cell niche, pericytes, ENDOTHELIAL-CELLS, CANCER, BRAIN, NEUROGENESIS, ANGIOGENESIS, GROWTH, ANTIANGIOGENESIS, GLIOBLASTOMA, MECHANISMS, STRATEGIES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1330943
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