Abstract：
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Phoenix TN,Patmore DM,Boop S,Boulos N,Jacus MO,Patel YT,Roussel MF,Finkelstein D,Goumnerova L,Perreault S,Wadhwa E,Cho YJ,Stewart CF,Gilbertson RJdoi
10.1016/j.ccell.2016.03.002subject
Has Abstractpub_date
2016-04-11 00:00:00pages
508-522issue
4eissn
1535-6108issn
1878-3686pii
S1535-6108(16)30055-1journal_volume
29pub_type
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