Proteomic Analysis Reveals Drug Accessible Cell Surface N-Glycoproteins of Primary and Established Glioblastoma Cell Lines
Proteomic Analysis Reveals Drug Accessible Cell Surface N-Glycoproteins of Primary and Established Glioblastoma Cell Lines
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DOI：
10.1021/pr300360a
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发表时间：
2012-10-01
影响因子：
4.4
通讯作者：
Wollscheid, Bernd
中科院分区：
文献类型：
--
作者：
Bock, Thomas;Moest, Hansjoerg;Wollscheid, Bernd
胶质母细胞瘤是成人中最常见的原发性胶质母细胞瘤细胞表面捕获型脑肿瘤，诊断后平均生存时间较低。为了改善胶质母细胞瘤的治疗，需要确定新的药物可及靶点。细胞表面糖蛋白由于其在癌细胞表面的可及性而成为主要的药物靶标。为了克服用于细胞表面蛋白检测的合适抗体的有限可用性，我们对胶质母细胞瘤表面组进行了全面的质谱研究。我们对原代离体胶质母细胞瘤细胞系与已建立的胶质母细胞瘤细胞系的组合细胞表面捕获分析揭示了633个N-糖蛋白，这极大地扩展了亚细胞分辨率下表面组药物靶点的已知数据。我们提供了直接的证据，常见的胶质母细胞瘤细胞表面糖蛋白和其丰度的近似估计，不能从基因组和/或转录组胶质母细胞瘤研究的信息。除了我们已经和潜在的药物可及的细胞表面糖蛋白的药学上有价值的剧目，我们建立了一个基于质谱的工具箱，使定向，灵敏和重复的糖蛋白测量的临床随访研究。所包含的Skyline胶质母细胞瘤SRM测定文库为在未来的药物扰动实验中平行检测检测到的胶质母细胞瘤表面组成员的丰度水平提供了更高的起点。
Glioblastoma is the most common primary Glioblastoma Cell Surface Capturing brain tumor in adults with low average survival time after diagnosis. In order to improve glioblastoma treatment, new drug-accessible targets need to be identified. Cell surface glycoproteins are prime drug targets due to their accessibility at the surface of cancer cells. To overcome the limited availability of suitable antibodies for cell surface protein detection, we performed a comprehensive mass spectrometric investigation of the glioblastoma surfaceome. Our combined cell surface capturing analysis of primary ex vivo glioblastoma cell lines in combination with established glioblastoma cell lines revealed 633 N-glycoproteins, which vastly extends the known data of surfaceome drug targets at subcellular resolution. We provide direct evidence of common glioblastoma cell surface glycoproteins and an approximate estimate of their abundances, information that could not be derived from genomic and/or transcriptomic glioblastoma studies. Apart from our pharmaceutically valuable repertoire of already and potentially drug-accessible cell surface glycoproteins, we built a mass-spectrometry-based toolbox enabling directed, sensitive, and repetitive glycoprotein measurements for clinical follow-up studies. The included Skyline Glioblastoma SRM assay library provides an elevated starting point for parallel testing of the abundance level of the detected glioblastoma surfaceome members in future drug perturbation experiments.