Journal of Neuro-Oncology

, Volume 115, Issue 2, pp 161–168 | Cite as

Neuropilin-2 contributes to tumorigenicity in a mouse model of Hedgehog pathway medulloblastoma

  • Melanie G. Hayden Gephart
  • YouRong Sophie Su
  • Samuel Bandara
  • Feng-Chiao Tsai
  • Jennifer Hong
  • Nicholas Conley
  • Helen Rayburn
  • Ljiljana Milenkovic
  • Tobias Meyer
  • Matthew P. Scott
Laboratory Investigation

Abstract

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.

Keywords

Neuropilin Hedgehog pathway Medulloblastoma Proliferation Brain tumor Pediatric 

Notes

Acknowledgments

MHG is supported by a post-doctoral fellowship from the California Institute of Regenerative Medicine (TG2-01159). This work was supported in part by NIH RO1 GM095948, and the Center for Children’s Brain Tumors (CCBT) of the Stanford School of Medicine and Lucile Packard Children’s Hospital. MPS is an Investigator of the Howard Hughes Medical Institute. We appreciate the thoughtful editing of the manuscript by E. Epstein.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Melanie G. Hayden Gephart
    • 1
    • 2
    • 3
    • 4
    • 6
  • YouRong Sophie Su
    • 2
    • 3
    • 4
  • Samuel Bandara
    • 5
  • Feng-Chiao Tsai
    • 5
  • Jennifer Hong
    • 7
  • Nicholas Conley
    • 2
    • 3
    • 4
    • 6
  • Helen Rayburn
    • 2
    • 3
    • 4
    • 6
  • Ljiljana Milenkovic
    • 2
    • 3
    • 4
    • 8
  • Tobias Meyer
    • 5
  • Matthew P. Scott
    • 2
    • 3
    • 4
    • 6
    • 8
  1. 1.Department of NeurosurgeryStanford University School of MedicineStanfordUSA
  2. 2.Department of Developmental BiologyStanford University School of MedicineStanfordUSA
  3. 3.Department of BioengineeringStanford University School of MedicineStanfordUSA
  4. 4.Department of GeneticsStanford University School of MedicineStanfordUSA
  5. 5.Department of Chemical and Systems BiologyStanford University School of MedicineStanfordUSA
  6. 6.Center for Children’s Brain TumorsLucile Packard Children’s Hospital, Stanford University School of MedicineStanfordUSA
  7. 7.Department of NeurosurgeryDartmouth-Hitchcock Medical CenterLebanonUSA
  8. 8.Howard Hughes Medical InstituteChevy ChaseUSA

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