肿瘤微环境中恶性生长的血管对肿瘤生长和转移有重要作用。外泌体是细胞分泌的微小囊泡，介导细胞间信号传递。研究发现，癌细胞可分泌外泌体携带长链非编码RNA（lncRNA）作用于其他靶细胞。鉴于胃癌抗血管治疗疗效极为有限，本课题着眼于胃癌外泌体对血管内皮细胞的调控机制。临床筛查发现胃癌外泌体中有一组lncRNAs 升高显著，其中一种lncRNA可结合与肿瘤血管生成相关的miR-29a/c，被称为lncR-angio。细胞实验表明胃癌外泌体可携带lncR-angio进入血管内皮细胞,吸附29a/c并激活其下游靶基因VEGF，促进内皮细胞增值及迁移。本课题通过运用外泌体提取、外泌体与细胞共培养、小鼠尾静脉注射外泌体技术等技术手段，证明外泌体lncR-angio与miR-29a/c 和VEGF组成的跨细胞通路参与肿瘤血管生成的新机制；并尝试运用外泌体作为运输工具靶向lncR-angio抑制肿瘤血管。

In the microenvironment of tumor, cancer cells can regulate angiogenesis, and the malignant growth of blood vessels plays a key role in the proliferation and metastasis of tumors. Recent studies found that secreted exosomes from cancer cells can transport lncRNAs to work in target cells. Considering that the effect of anti-angiogenesis therapy in gastric cancer(GC) is limited, the current study is focused on the regulation of GC secreted exosomes on vascular endothelial cells. Base on clinical screening, we found a panel of exosome-lncRNAs is clearly up-regulated in gastric cancer, and one was named for its interaction with miR-29a/c, which is closely related to angiogenesis. In vitro experiments showed GC exosomes can transport lncR-angio into vascular endothelial cells,and lncR-angio adsorbs miR-29a/c and activates VEGF, thus promoting proliferation and migration of vascular endothelial cells. The current study is designed to find that GC-exosomes transport lncR-angio can regulate the process of angiogenesis by targeting the miR-29a/c-VEGF pathway both in vivo and in vitro, and explore the novel regulatory mechanism of angiogenesis in tumor microenvironment. Moreover, we will try to inhibit angiogenesis in gastric cancer by using anti-lncR-angio.The current study reveals the novel mechanism of angiogenesis and illustrates a new direction in clinical treatment.