TY - JOUR
T1 - Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype
AU - Phoenix, Timothy N.
AU - Patmore, Deanna M.
AU - Boop, Scott
AU - Boulos, Nidal
AU - Jacus, Megan O.
AU - Patel, Yogesh T.
AU - Roussel, Martine F.
AU - Finkelstein, David
AU - Goumnerova, Liliana
AU - Perreault, Sebastien
AU - Wadhwa, Elizabeth
AU - Cho, Yoon Jae
AU - Stewart, Clinton F.
AU - Gilbertson, Richard J.
N1 - Funding Information:
This work was supported by grants from the NIH (R.J.G., P01CA96832 and P30CA021765 ), the American Lebanese Syrian Associated Charities and Cancer Research UK . We are grateful to the staff of the Hartwell Center for Bioinformatics and Biotechnology, the Cell and Tissue Imaging Shared Resource, and the ARC at St Jude Children's Research Hospital for technical assistance.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/4/11
Y1 - 2016/4/11
N2 - The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors.
AB - The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors.
UR - http://www.scopus.com/inward/record.url?scp=84962094334&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962094334&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2016.03.002
DO - 10.1016/j.ccell.2016.03.002
M3 - Article
C2 - 27050100
AN - SCOPUS:84962094334
VL - 29
SP - 508
EP - 522
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 4
ER -