Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma.
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Embargo End Date
ICR Authors
Authors
Qin, EY
Cooper, DD
Abbott, KL
Lennon, J
Nagaraja, S
Mackay, A
Jones, C
Vogel, H
Jackson, PK
Monje, M
Cooper, DD
Abbott, KL
Lennon, J
Nagaraja, S
Mackay, A
Jones, C
Vogel, H
Jackson, PK
Monje, M
Document Type
Journal Article
Date
2017-08-24
Date Accepted
2017-07-13
Abstract
The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knock down starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion. PAPERCLIP.
Citation
Cell, 2017, 170 (5), pp. 845 - 859.e19
Source Title
Publisher
CELL PRESS
ISSN
0092-8674
eISSN
1097-4172
Collections
Research Team
Glioma Team