A Perivascular Niche for Brain Tumor Stem Cells

Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain th...

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Bibliographic Details
Published in:Cancer cell 2007, Vol.11 (1), p.69-82
Main Authors: Calabrese, Christopher, Poppleton, Helen, Kocak, Mehmet, Hogg, Twala L., Fuller, Christine, Hamner, Blair, Oh, Eun Young, Gaber, M. Waleed, Finklestein, David, Allen, Meredith, Frank, Adrian, Bayazitov, Ildar T., Zakharenko, Stanislav S., Gajjar, Amar, Davidoff, Andrew, Gilbertson, Richard J.
Format: Article
Language:English
Subjects:
AC133 Antigen
Animals
Antigens, CD - metabolism
Brain Neoplasms - blood supply
Brain Neoplasms - metabolism
Cell Communication - physiology
Cells, Cultured
Coculture Techniques
Endothelial Cells - metabolism
Female
Gene Expression
Glycoproteins - metabolism
Image Processing, Computer-Assisted
Immunohistochemistry
In Situ Hybridization, Fluorescence
Mice
Mice, Nude
Neoplastic Stem Cells - metabolism
Neurons - metabolism
Neurons - pathology
Peptides - metabolism
STEMCELL
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Summary:Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2006.11.020