Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype

Timothy N. Phoenix, Deanna M. Patmore, Scott Boop, Nidal Boulos, Megan O. Jacus, Yogesh T. Patel, Martine F. Roussel, David Finkelstein, Liliana Goumnerova, Sebastien Perreault, Elizabeth Wadhwa, Yoon-Jae Cho, Clinton F. Stewart, Richard J. Gilbertson

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)508-522
Number of pages15
JournalCancer Cell
Volume29
Issue number4
DOIs
StatePublished - Apr 11 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Phoenix, T. N., Patmore, D. M., Boop, S., Boulos, N., Jacus, M. O., Patel, Y. T., Roussel, M. F., Finkelstein, D., Goumnerova, L., Perreault, S., Wadhwa, E., Cho, Y-J., Stewart, C. F., & Gilbertson, R. J. (2016). Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. Cancer Cell, 29(4), 508-522. https://doi.org/10.1016/j.ccell.2016.03.002