膜蛋白糖基化修饰调控神经母细胞瘤转移及其机制研究

转移是限制神经母细胞瘤（neuroblastoma，NB）患儿疗效及预后的重要原因，阐明NB转移分子机制并探寻新的治疗靶点抑制转移，这将对改善NB预后具有重要的基础理论意义和临床应用价值。胞膜蛋白异常糖基化修饰在肿瘤转移形成中发挥重要作用，也是肿瘤治疗的热门靶点。目前蛋白糖基化介导NB转移备受关注，但这些研究多基于与成人肿瘤相关的特定糖基转移酶基因或是靶蛋白进行分析，对NB糖链、糖基转移酶和蛋白糖基化修饰位点等缺乏系统性的鉴定。基于此，本项目拟以凝集素芯片结合质谱检测技术，从糖基化蛋白种类和表达丰度、糖基化位点及糖链组成、糖基转移酶表达谱这三个方面系统性解析NB细胞胞膜蛋白糖基化修饰在介导转移中的作用及其潜在机制，并筛选出可作为潜在NB治疗靶点的胞膜糖蛋白，为NB的临床治疗提供一种新型有效手段。

Metastasis is an important reason for limiting the treatment efficiency and prognosis of children with neuroblastoma (NB). Thus, elucidating the molecular mechanism and exploring novel therapeutic targets to inhibit NB metastasis will be important for theoretical development and improvement of NB prognosis. Abnormal glycosylation of membrane proteins plays important roles in metastasis and is potential therapeutic targets for clinical application. At present, protein glycosylation-mediated NB transfer has attracted much attention, but these studies are mostly based on the analysis of specific glycosyltransferase genes or target proteins associated with adult tumors. Lack of systematic identification of NB sugar chains, glycosyltransferases, and protein glycosylation modification sites. In this study, we propose to systematically identify the varieties, expression abundance, composition of glycosites and sugar chain of glycoproteins, and expression profiles of glycotransferases in NB metastatic cells by combining lectin-microarray and mass spectrometry. Membrane glycoproteins involved in NB metastasis will be selected, and their function will be evaluated by using bioinformatics and molecular studies. The current study will clarify the key glycoproteins in NB metastasis, provide potential therapeutic targets and design a novel strategy for NB therapy.