Garcia Jacob, Faca Vitor, Jarzembowski Jason, Zhang Qing, Park Julie, Hanash Samir
Children's Hospital and Research Center at Oakland, California 94609, USA.
J Proteome Res. 2009 Aug;8(8):3791-6. doi: 10.1021/pr800964v.
Neuroblastoma tumors are derived from the neural crest and exhibit substantial phenotypic heterogeneity and various degrees of differentiation and maturation. The identification of new cell surface markers in neuroblastoma has relevance to disease classification and therapy. As a means to categorize neuroblastomas based on cell surface protein expression, we have obtained a comprehensive profile of the cell surface proteome of the MYCN nonamplified SH-SY5Y neuroblastoma cell line. Biotinylated cell surface proteins were captured using an avidin affinity column, fractionated by reversed-phase chromatography and subjected to in-depth analysis by LC-MS/MS. An extensive list of proteins was established and a subset of surface membrane proteins was assessed by immunohistochemistry in a set of neuroblastoma tissue microarrays. Among identified proteins tested, NCAM and CD147 exhibited increased expression in poorly differentiated tumors (p < 0.01 and <0.03, respectively). CD147 expression was previously associated with aggressive carcinomas but has not been described in neuroblastoma. This comprehensive neuroblastoma cell surface profile has identified novel potential markers for neuroblastoma classification and novel potential targets for therapy.
神经母细胞瘤肿瘤起源于神经嵴，表现出显著的表型异质性以及不同程度的分化和成熟。神经母细胞瘤中新细胞表面标志物的鉴定与疾病分类及治疗相关。作为基于细胞表面蛋白表达对神经母细胞瘤进行分类的一种方法，我们获得了MYCN未扩增的SH-SY5Y神经母细胞瘤细胞系细胞表面蛋白质组的全面概况。使用抗生物素蛋白亲和柱捕获生物素化的细胞表面蛋白，通过反相色谱法进行分离，并通过液相色谱-串联质谱法进行深入分析。建立了一份广泛的蛋白质清单，并在一组神经母细胞瘤组织微阵列中通过免疫组织化学评估了表面膜蛋白的一个子集。在所测试的已鉴定蛋白质中，神经细胞黏附分子（NCAM）和CD147在低分化肿瘤中表达增加（分别为p < 0.01和<0.03）。CD147表达先前与侵袭性癌相关，但在神经母细胞瘤中尚未见报道。这种全面的神经母细胞瘤细胞表面概况已经鉴定出用于神经母细胞瘤分类的新型潜在标志物和用于治疗的新型潜在靶点。
