Title: Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma
Authors: Snuderl, Matija
Batista, Ana
Kirkpatrick, Nathaniel D
Ruiz de Almodovar, Carmen
Riedemann, Lars
Walsh, Elisa C
Anolik, Rachel
Huang, Yuhui
Martin, John D
Kamoun, Walid
Knevels, Ellen
Schmidt, Thomas
Farrar, Christian T
Vakoc, Benjamin J
Mohan, Nishant
Chung, Euiheon
Roberge, Sylvie
Peterson, Teresa
Bais, Carlos
Zhelyazkova, Boryana H
Yip, Stephen
Hasselblatt, Martin
Rossig, Claudia
Niemeyer, Elisabeth
Ferrara, Napoleone
Klagsbrun, Michael
Duda, Dan G
Fukumura, Dai
Xu, Lei
Carmeliet, Peter
Jain, Rakesh K # ×
Issue Date: Feb-2013
Publisher: MIT Press
Series Title: Cell vol:152 issue:5 pages:1065-76
Article number: 10.1016/j.cell.2013.01.036
Abstract: Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and are associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas, independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastasis, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1-and not vascular endothelial growth factor receptor 1-to promote tumor cell survival. This critical tumor-stroma interaction-mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes-supports the development of therapies targeting PlGF/Nrp1 pathway.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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