Thomas Stacey L, De Vries George H
Research Service, Edward Hines Jr. V.A. Hospital, 5th Avenue and Roosevelt Road, Hines, IL 60141, USA.
Neurochem Res. 2007 Jul;32(7):1129-41. doi: 10.1007/s11064-007-9279-z. Epub 2007 Apr 3.
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.
患有1型神经纤维瘤病（NF1）的个体的周围神经鞘瘤血管高度丰富，并且含有神经纤维瘤蛋白缺陷的施万细胞。本研究检测了神经纤维瘤蛋白缺陷的人施万细胞相对于正常人施万细胞的血管生成表达谱，对促血管生成因子和抗血管生成因子进行了表征。神经纤维瘤蛋白缺陷的施万细胞系的条件培养基具有促血管生成作用，这可通过其刺激内皮细胞增殖和迁移的能力得到证明。通过基因芯片和蛋白质芯片分析，我们发现相对于正常人施万细胞，神经纤维瘤蛋白缺陷的施万细胞中促血管生成因子表达增加，抗血管生成因子表达减少。神经纤维瘤蛋白缺陷的施万细胞还表现出几种生长因子受体的表达增加以及一种整合素的表达减少。我们得出结论，神经纤维瘤蛋白缺陷的施万细胞中促血管生成因子、抗血管生成因子、生长因子受体和一种整合素的表达失调。这些失调的分子可能有助于NF1周围神经鞘瘤的生长和进展。
