Expression data of endothelial cells from mouse hindbrain and genetic Wnt-medulloblastoma and Shh-medulloblastoma mouse models

The childhood brain tumour medulloblastoma includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant Beta-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-tumoural chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma a less curable disease subtype contains an intact blood brain barrier, rendering this tumour impermeable and resistant to chemotherapy. Remarkably, the medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumour vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumours.

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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 RJ