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 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.
Calabrese
Christopher
C
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Poppleton
Helen
H
Kocak
Mehmet
M
Hogg
Twala L
TL
Fuller
Christine
C
Hamner
Blair
B
Oh
Eun Young
EY
Gaber
M Waleed
MW
Finklestein
David
D
Allen
Meredith
M
Frank
Adrian
A
Bayazitov
Ildar T
IT
Zakharenko
Stanislav S
SS
Gajjar
Amar
A
Davidoff
Andrew
A
Gilbertson
Richard J
RJ
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
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides