Inhibition of medulloblastoma cell invasion by Slit

T. E. Werbowetski-Ogilvie, M. Seyed Sadr, N. Jabado, A. Angers-Loustau, N. Y.R. Agar, J. Wu, R. Bjerkvig, J. P. Antel, D. Faury, Y. Rao*, R. F. Del Maestro

*Corresponding author for this work

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Invasion of brain tumor cells has made primary malignant brain neoplasms among the most recalcitrant to therapeutic strategies. We tested whether the secreted protein Slit2, which guides the projection of axons and developing neurons, could modulate brain tumor cell invasion. Slit2 inhibited the invasion of medulloblastoma cells in a variety of in vitro models. The effect of Slit2 was inhibited by the Robo ectodomain. Time-lapse videomicroscopy indicated that Slit2 reduced medulloblastoma invasion rate without affecting cell direction or proliferation. Both medulloblastoma and glioma tumors express Robo1 and Slit2, but only medulloblastoma invasion is inhibited by recombinant Slit2 protein. Downregulation of activated Cdc42 may contribute to this differential response. Our findings reinforce the concept that neurodevelopmental cues such as Slit2 may provide insights into brain tumor invasion.

Original languageEnglish (US)
Pages (from-to)5103-5112
Number of pages10
JournalOncogene
Volume25
Issue number37
DOIs
StatePublished - Aug 24 2006

Keywords

  • Glioma
  • Inhibitor
  • Invasion
  • Medulloblastoma
  • Slit

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Werbowetski-Ogilvie, T. E., Seyed Sadr, M., Jabado, N., Angers-Loustau, A., Agar, N. Y. R., Wu, J., Bjerkvig, R., Antel, J. P., Faury, D., Rao, Y., & Del Maestro, R. F. (2006). Inhibition of medulloblastoma cell invasion by Slit. Oncogene, 25(37), 5103-5112. https://doi.org/10.1038/sj.onc.1209524