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Angiogenic Expression Profile of Normal and Neurofibromin-Deficient Human Schwann Cells

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Abstract

Peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are highly vascular and contain Schwann cells which are deficient in neurofibromin. This study examines the angiogenic expression profile of neurofibromin-deficient human Schwann cells relative to normal human Schwann cells, characterizing both pro-angiogenic and anti-angiogenic factors. Conditioned media from neurofibromin-deficient Schwann cell lines was pro-angiogenic as evidenced by its ability to stimulate endothelial cell proliferation and migration. Using gene array and protein array analysis, we found increased expression of pro-angiogenic factors and decreased expression of anti-angiogenic factors in neurofibromin-deficient Schwann cells relative to normal human Schwann cells. Neurofibromin-deficient Schwann cells also showed increased expression of several growth factor receptors and decreased expression of an integrin. We conclude that neurofibromin-deficient Schwann cells have dysregulated expression of pro-angiogenic factors, anti-angiogenic factors, growth factor receptors, and an integrin. These dysregulated molecules may contribute to the growth and progression of NF1 peripheral nerve sheath tumors.

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Acknowledgments

We are grateful to Dr. Patrick Wood for providing the human peripheral nerve and Dr. David Muir for providing the NF1 tumor-derived Schwann cell lines. We thank Dr. Ian Dang for his guidance. We also thank Jean Egerman and Susan MacPhee-Gray for editorial assistance. S.L. Thomas was supported by a fellowship from the Arthur J. Schmitt Foundation. This work was supported by grants from Illinois NF, Inc. and Minnesota NF, Inc.

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Authors and Affiliations

  1. Research Service, Edward Hines Jr. V.A. Hospital, 5th Avenue and Roosevelt Road, Hines, IL, 60141, USA

    Stacey L. Thomas & George H. De Vries

  2. Neuroscience Program, Loyola University Medical Center, Maywood, IL, USA

    Stacey L. Thomas

  3. Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL, USA

    Stacey L. Thomas & George H. De Vries

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  1. Stacey L. Thomas
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  2. George H. De Vries
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Correspondence to George H. De Vries.

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Thomas, S.L., De Vries, G.H. Angiogenic Expression Profile of Normal and Neurofibromin-Deficient Human Schwann Cells. Neurochem Res 32, 1129–1141 (2007). https://doi.org/10.1007/s11064-007-9279-z

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  • DOI: https://doi.org/10.1007/s11064-007-9279-z

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