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Slit2 involvement in glioma cell migration is mediated by Robo1 receptor

  • Lab. Investigation-human/animal tissue
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Abstract

Slit and Robo proteins are evolutionarily conserved molecules whose interaction underlies axon guidance and neuronal precursor cell migration. During development secreted Slit proteins mediate chemorepulsive signals on cells expressing Robo receptors. Because similar molecular mechanisms may be utilized in glioma cell invasion and neuroblast migration, we studied the expression of Slit2 and its transmembrane receptor Robo1 as well as their functional role in migration in glioma cells. qRT-PCR and immunohistochemistry of human specimens revealed that Slit2 was distinctly expressed by non-neoplastic neurons, but at only very low levels in fibrillary astrocytoma and glioblastoma. Robo1 also was mainly restricted to neurons in the normal brain, whereas astrocytic tumor cells in situ as well as glioblastoma cell lines overexpressed Robo1 at mRNA and protein levels. Recombinant human Slit2 in a concentration of 0.45 nM was repulsive for glioma cell lines in a modified Boyden chamber assay. RNAi-mediated knockdown of Robo1 in glioma cell lines neutralized the repulsive effect of Slit2, demonstrating that Robo1 served as the major Slit2 receptor. Our findings suggest that a chemorepulsive effect mediated by interaction of Slit2 and Robo1 participates in glioma cell guidance in the brain.

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Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (grant SFB 629 B5) and the Wilhelm-Sander-Stiftung (grant 2005.058.1).

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Authors and Affiliations

  1. Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48149, Münster, Germany

    Sonja Mertsch, Nicole Schmitz, Astrid Jeibmann, Werner Paulus & Volker Senner

  2. Vascular Biology Center, University of Minnesota Medical School, Minneapolis, MN, USA

    Jian-Guo Geng

Authors
  1. Sonja Mertsch
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  2. Nicole Schmitz
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  3. Astrid Jeibmann
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  4. Jian-Guo Geng
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  5. Werner Paulus
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  6. Volker Senner
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Correspondence to Werner Paulus.

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Mertsch, S., Schmitz, N., Jeibmann, A. et al. Slit2 involvement in glioma cell migration is mediated by Robo1 receptor. J Neurooncol 87, 1–7 (2008). https://doi.org/10.1007/s11060-007-9484-2

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  • DOI: https://doi.org/10.1007/s11060-007-9484-2

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