Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 115, Issue 2, Pages 161-168Publisher
SPRINGER
DOI: 10.1007/s11060-013-1216-1
Keywords
Neuropilin; Hedgehog pathway; Medulloblastoma; Proliferation; Brain tumor; Pediatric
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Funding
- California Institute of Regenerative Medicine [TG2-01159]
- NIH [RO1 GM095948]
- Center for Children Brain Tumors (CCBT) of the Stanford School of Medicine
- Center for Children Brain Tumors (CCBT) of the Lucile Packard Children's Hospital
- Howard Hughes Medical Institute
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The Hedgehog (Hh) signaling pathway has been implicated in the most common childhood brain tumor, medulloblastoma (MB). Given the toxicity of post-surgical treatments for MB, continued need exists for new, targeted therapies. Based upon our finding that Neuropilin (Nrp) transmembrane proteins are required for Hh signal transduction, we investigated the role of Nrp in MB cells. Cultured cells derived from a mouse Ptch (+/-) ;LacZ MB (Med1-MB), effectively modeled the Hh pathway-related subcategory of human MBs in vitro. Med1-MB cells maintained constitutively active Hh target gene transcription, and consistently formed tumors within one month after injection into mouse cerebella. The proliferation rate of Med1-MBs in culture was dependent upon Nrp2, while reducing Nrp1 function had little effect. Knockdown of Nrp2 prior to cell implantation significantly increased mouse survival, compared to transfection with a non-targeting siRNA. Knocking down Nrp2 specifically in MB cells avoided any direct effect on tumor vascularization. Nrp2 should be further investigated as a potential target for adjuvant therapy in patients with MB.
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