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 language | English (US) |
|---|---|
| Pages (from-to) | 508-522 |
| Number of pages | 15 |
| Journal | Cancer Cell |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 11 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
Cite this
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 journal › Article
}
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.
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 -