title: A perivascular niche for brain tumor stem cells.
abstract: 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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Calabrese
authors.forename: Helen
authors.initials: H
authors.lastname: Poppleton
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Twala L
authors.initials: TL
authors.lastname: Hogg
authors.forename: Christine
authors.initials: C
authors.lastname: Fuller
authors.forename: Blair
authors.initials: B
authors.lastname: Hamner
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Oh
authors.forename: M Waleed
authors.initials: MW
authors.lastname: Gaber
authors.forename: David
authors.initials: D
authors.lastname: Finklestein
authors.forename: Meredith
authors.initials: M
authors.lastname: Allen
authors.forename: Adrian
authors.initials: A
authors.lastname: Frank
authors.forename: Ildar T
authors.initials: IT
authors.lastname: Bayazitov
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Zakharenko
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Andrew
authors.initials: A
authors.lastname: Davidoff
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides