Angiogenic expression profile of normal and neurofibromin-deficient human Schwann cells.
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.
Thomas
Stacey L
SL
Research Service, Edward Hines Jr. V.A. Hospital, 5th Avenue and Roosevelt Road, Hines, IL 60141, USA.
De Vries
George H
GH
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D017077:Culture Media, Conditioned; D025542:Neurofibromin 1