title: Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma.
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.
authors: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Matija
authors: M
authors: Snuderl
authors: Ana
authors: A
authors: Batista
authors: Nathaniel D
authors: ND
authors: Kirkpatrick
authors: Carmen
authors: C
authors: Ruiz de Almodovar
authors: Lars
authors: L
authors: Riedemann
authors: Elisa C
authors: EC
authors: Walsh
authors: Rachel
authors: R
authors: Anolik
authors: Yuhui
authors: Y
authors: Huang
authors: John D
authors: JD
authors: Martin
authors: Walid
authors: W
authors: Kamoun
authors: Ellen
authors: E
authors: Knevels
authors: Thomas
authors: T
authors: Schmidt
authors: Christian T
authors: CT
authors: Farrar
authors: Benjamin J
authors: BJ
authors: Vakoc
authors: Nishant
authors: N
authors: Mohan
authors: Euiheon
authors: E
authors: Chung
authors: Sylvie
authors: S
authors: Roberge
authors: Teresa
authors: T
authors: Peterson
authors: Carlos
authors: C
authors: Bais
authors: Boryana H
authors: BH
authors: Zhelyazkova
authors: Stephen
authors: S
authors: Yip
authors: Martin
authors: M
authors: Hasselblatt
authors: Claudia
authors: C
authors: Rossig
authors: Elisabeth
authors: E
authors: Niemeyer
authors: Napoleone
authors: N
authors: Ferrara
authors: Michael
authors: M
authors: Klagsbrun
authors: Dan G
authors: DG
authors: Duda
authors: Dai
authors: D
authors: Fukumura
authors: Lei
authors: L
authors: Xu
authors: Peter
authors: P
authors: Carmeliet
authors: Rakesh K
authors: RK
authors: Jain
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002528:Cerebellar Neoplasms / Q000378:metabolism / Q000473:pathology*; D002531:Cerebellum / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D039942:Neuropilin-1 / Q000378:metabolism*; D019899:Paracrine Communication; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D039942:Neuropilin-1; D040281:Vascular Endothelial Growth Factor Receptor-1