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Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells

Oncogene volume 26, pages 5752–5761 (2007)Cite this article

Abstract

The hedgehog (Hh) signaling pathway regulates progenitor cells during embryogenesis and tumorigenesis in multiple organ systems. We have investigated the activity of this pathway in adult gliomas, and demonstrate that the Hh pathway is operational and activated within grade II and III gliomas, but not grade IV de novo glioblastoma multiforme. Furthermore, our studies reveal that pathway activity and responsiveness is confined to progenitor cells within these tumors. Additionally, we demonstrate that Hh signaling in glioma progenitor cells is ligand-dependent and provide evidence documenting the in vivo source of Sonic hedgehog protein. These findings suggest a regulatory role for the Hh pathway in progenitor cells within grade II and III gliomas, and the potential clinical utility of monitoring and targeting this pathway in these primary brain tumors.

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Acknowledgements

We are grateful to Peter Konrad, Matthew Pearson and Kyle Weaver for brain specimens, to Ken Niermann, John Floyd, Khubaib Mapara, Karen Deal, Larry Pierce, Charles Stevenson and Justin Bachmann for sample collections, Darren Orten, Sam Saleh and Vandana Grover for synthesis of SAG and Michael Edgeworth for assistance with statistical analyses. This work was supported by grants from the NINDS (R01 NS051557, ME and K08 NS02133, MKC), the Burroughs Wellcome Fund (MKC) and the Doris Duke Charitable Foundation (MKC).

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Author notes

  1. M Ehtesham, A Sarangi and J G Valadez: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA

    M Ehtesham, S Chanthaphaychith & R C Thompson

  2. Department of Cancer Biology, Vanderbilt Medical Center, Nashville, TN, USA

    M Ehtesham

  3. Vanderbilt Ingram Cancer Center, Vanderbilt Medical Center, Nashville, TN, USA

    M Ehtesham & R C Thompson

  4. Department of Neurology, Vanderbilt Medical Center, Nashville, TN, USA

    A Sarangi, J G Valadez & M K Cooper

  5. Department of Pathology, Vanderbilt Medical Center, Nashville, TN, USA

    M W Becher & T W Abel

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  1. M Ehtesham
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  2. A Sarangi
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  3. J G Valadez
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  4. S Chanthaphaychith
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  5. M W Becher
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  6. T W Abel
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  7. R C Thompson
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  8. M K Cooper
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Corresponding author

Correspondence to M K Cooper.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ehtesham, M., Sarangi, A., Valadez, J. et al. Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells. Oncogene 26, 5752–5761 (2007). https://doi.org/10.1038/sj.onc.1210359

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