1. Maturation of tumor vasculature by interferon-beta disrupts the vascular niche of glioma stem cells
- Author
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R F, Williams, T L, Sims, L, Tracey, A L, Myers, C Y C, Ng, H, Poppleton, A C, Nathwani, and A M, Davidoff
- Subjects
Male ,Brain Neoplasms ,Endothelial Cells ,Fluorescent Antibody Technique ,Antineoplastic Agents ,Cell Communication ,Glioma ,Interferon-beta ,Mice, SCID ,Xenograft Model Antitumor Assays ,Coculture Techniques ,Mice ,Neoplastic Stem Cells ,Animals ,Humans ,Pericytes - Abstract
The vascular niche necessary for cancer stem cell maintenance is a potential target for cancer therapy.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.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.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.
- Published
- 2010