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

65 Citations (Scopus)

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

Fingerprint

Medulloblastoma
Blood-Brain Barrier
Genotype
Phenotype
Drug Therapy
Brain Neoplasms
Catenins
Permeability
Neoplasms
Endothelial Cells

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., ... 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

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

In: Cancer Cell, Vol. 29, No. 4, 11.04.2016, p. 508-522.

Research output: Contribution to journalArticle

Phoenix, TN, Patmore, DM, Boop, S, Boulos, N, Jacus, MO, Patel, YT, Roussel, MF, Finkelstein, D, Goumnerova, L, Perreault, S, Wadhwa, E, Cho, Y-J, Stewart, CF & Gilbertson, RJ 2016, 'Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype', Cancer Cell, vol. 29, no. 4, pp. 508-522. https://doi.org/10.1016/j.ccell.2016.03.002
Phoenix TN, Patmore DM, Boop S, Boulos N, Jacus MO, Patel YT et al. Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. Cancer Cell. 2016 Apr 11;29(4):508-522. https://doi.org/10.1016/j.ccell.2016.03.002
Phoenix, Timothy N. ; Patmore, Deanna M. ; Boop, Scott ; Boulos, Nidal ; Jacus, Megan O. ; Patel, Yogesh T. ; Roussel, Martine F. ; Finkelstein, David ; Goumnerova, Liliana ; Perreault, Sebastien ; Wadhwa, Elizabeth ; Cho, Yoon-Jae ; Stewart, Clinton F. ; Gilbertson, Richard J. / Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. In: Cancer Cell. 2016 ; Vol. 29, No. 4. pp. 508-522.
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