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Publication Detail
Maturation of tumor vasculature by interferon-beta disrupts the vascular niche of glioma stem cells
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Williams RF, Sims TL, Tracey L, Myers AL, Ng CY, Poppleton H, Nathwani AC, Davidoff AM
  • Publication date:
    09/2010
  • Pagination:
    3301, 3308
  • Journal:
    Anticancer Res.
  • Volume:
    30
  • Issue:
    9
  • Keywords:
    Animals, Antineoplastic Agents, blood supply, Brain Neoplasms, Cell Communication, Coculture Techniques, drug effects, drug therapy, Endothelial Cells, Fluorescent Antibody Technique, Glioma, Humans, Interferon-beta, Male, metabolism, methods, Mice, Mice,Scid, Neoplastic Stem Cells, Pericytes, pharmacology, therapy, Xenograft Model Antitumor Assays
  • Author URL:
  • Notes:
    DA - 20101014 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't RN - 0 (Antineoplastic Agents) RN - 77238-31-4 (Interferon-beta) SB - IM
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 stem 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
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