Chen Hui-Ling, Seol Haeri, Brown Kristy Jean, Gordish-Dressman Heather, Hill Ashley, Gallo Vittorio, Packer Roger, Hathout Yetrib
Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
Int J Mol Sci. 2012;13(7):9380-9399. doi: 10.3390/ijms13079380. Epub 2012 Jul 24.
To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures. Inversely, 9 proteins displayed decreased levels in the conditioned media of NF1 relative to normal Schwann cells. The proteins with increased levels included proteins involved in cell growth, angiogenesis and complement pathway while proteins with decreased levels included those involved in cell adhesion, plasminogen pathway and extracellular matrix remodeling. Retinoic acid receptor responder protein-1 (RARRES1), previously described as an integral membrane tumor suppressor, was found exclusively secreted by NF1 Schwann cells but not by normal Schwann cells. All-trans retinoic acid modulated secretion of RARRES1 in a dose dependent manner. This study shows altered secretion of key proteins in NF1 derived Schwann cells. The potential implication of these proteins in neurofibroma biology is discussed.
为深入了解神经纤维瘤的生物化学特性，我们对从手术切除的丛状神经纤维瘤和正常神经组织中分离出的原代人雪旺细胞进行了全面的分泌组分析。通过结合SDS-PAGE和高精度LC-MS/MS，在雪旺细胞培养物的条件培养基中总共可靠地鉴定出907种蛋白质。无标记蛋白质组分析显示，相对于两种正常雪旺细胞培养物，NF1雪旺细胞培养物的四个生物学重复一致释放高水平的22种蛋白质。相反，相对于正常雪旺细胞，9种蛋白质在NF1的条件培养基中水平降低。水平升高的蛋白质包括参与细胞生长、血管生成和补体途径的蛋白质，而水平降低的蛋白质包括参与细胞粘附、纤溶酶原途径和细胞外基质重塑的蛋白质。维甲酸受体反应蛋白-1（RARRES1），先前被描述为一种完整膜肿瘤抑制因子，被发现仅由NF1雪旺细胞分泌，而正常雪旺细胞不分泌。全反式维甲酸以剂量依赖方式调节RARRES1的分泌。本研究显示NF1来源的雪旺细胞中关键蛋白质的分泌发生改变。并讨论了这些蛋白质在神经纤维瘤生物学中的潜在意义。
