Angiogenic expression profile of normal and neurofibromin-deficient human Schwann cells

Neurochem Res. 2007 Jul;32(7):1129-41. doi: 10.1007/s11064-007-9279-z. Epub 2007 Apr 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / metabolism
  • Angiogenic Proteins / genetics
  • Angiogenic Proteins / metabolism
  • Cell Movement / physiology
  • Cell Proliferation
  • Culture Media, Conditioned
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Gene Expression Profiling*
  • Humans
  • Molecular Sequence Data
  • Neovascularization, Pathologic*
  • Neovascularization, Physiologic*
  • Neurofibromatosis 1 / genetics
  • Neurofibromatosis 1 / metabolism
  • Neurofibromatosis 1 / pathology
  • Neurofibromin 1 / genetics
  • Neurofibromin 1 / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Protein Array Analysis
  • Schwann Cells / cytology
  • Schwann Cells / physiology*

Substances

  • Angiogenesis Inhibitors
  • Angiogenic Proteins
  • Culture Media, Conditioned
  • Neurofibromin 1