Syntenin（又称MDA9）是广泛存在于原核及真核生物中的胞内衔接蛋白(adaptor protein)。胶质母细胞瘤(GBM)是一种最常见的颅内恶性肿瘤。我们的初步实验表明，Syntenin在胶质瘤病人样本和细胞系中异常高表达，且其表达水平与GBM病人的生存率成负相关。RNAi干扰敲除Synteinin可抑制胶质瘤细胞增殖，而Syntenin的过表达可促进细胞生长。我们还发现，在多个胶质瘤细胞系中Syntenin蛋白可通过外泌体（exosome）途径大量分泌到胞外，且从高表达Syntenin的GBM细胞培养基中分离纯化的外泌体可明显促进GBM细胞的增殖和侵袭，并可促进脑血管内皮细胞的血管新生。本项目将在此基础上进一步研究Syntenin特别是其分泌蛋白在GBM发生发展中的生物学功能及分子机制，探讨其作为一个新的胶质瘤生物治疗靶点以及作为临床诊断和预后评价的新指标的可行性。

Syntenin, also called MDA9, is an intracellular PDZ domain containing adaptor protein that is ubiquously expressed among various animal species. Syntenin is a multifunctional protein due to its intercalation with various proteins. By in silico analyzing the the Cancer Genome Atlas (TCGA) and REMBRANDT database, we found SDCBP (encoding Syntein protein in humans) is significagtly upregulated in gliomas，especially in the most malignant type--glioblastoma multiforme (GBMs), and its expression is inversely correlated with the survival rate of GBM patients. Our preliminary data showed that Syntenin is indeed overexpressed at both mRNA and protein levels in a collection of GBM specimens and cell lines, and knockdown of Syntein using RNA interference approach dramatically inhibited cell proliferation, while over expression of Syntenin increased GBM cell growth. Furthermore, it was found that Syntenin is able to significantly secreted in multiple glioma cell lines mainly through exosome pathway. Functional experiments showed that the isolated exosomes from Syntenin overexpressing GBM cells is able to stimulate glioma cell proliferation and invasion, and enhance tube formation of the human brain microvascular endothelial cells (HBMEC) in vitro. All together, these results suggested that Syntenin might be a novel diagnosis/prognosis marker and therapeutic target gene in glioblastoma. This project will further investigate the biological function and molecular mechnisms of Syntenin especially its secreted protein in the gliomagenesis and development, and explore its possibility of being a novel therapeutic target and/or a novel marker for glioblastoma diagnosis and prognosis.