基于课题组前期建立的肿瘤微环境研究模型，本课题将探索微环境中间质细胞特异的lncRNA，及其外排体中包裹的lncRNA调控肿瘤转移的作用和机制。通过分离乳腺癌和食管癌临床标本的肿瘤间质细胞及其分泌的外排体系统筛选和鉴定间质细胞表达的及其外排体中包裹的lncRNA。通过检测细胞因子分泌和信号通路状态等探索lncRNA调控间质细胞激活的作用。通过细胞共培养体系，以及人源化小鼠和条件基因修饰小鼠探索间质细胞内的lncRNA调控其促肿瘤转移的作用；通过干预外排体中lncRNA的水平，探讨间质细胞通过外排体传导lncRNA调控肿瘤转移的作用和机制。并在临床肿瘤标本观察间质细胞lncRNA的表达，分析其与肿瘤转移和患者预后的关系。本课题将发现一批调控肿瘤间质细胞激活和促肿瘤转移的lncRNA，为揭示lncRNA作为穿梭细胞间的信号分子调节多种细胞功能的机制提供线索，并为靶向肿瘤微环境的治疗提供新靶点。

Based on established platforms for tumor micro-environment study, we will isolate stromal cells and exosomes secreted by them. We will then screen and identify lncRNAs expressed and secreted by stromal cells based on platforms established by sub-project 1. We will then explore the regulatory roles of lncRNAs in stromal cell activation by examine cytokine secretion and signal pathway status. By in vitro co-culture system and in vivo humanized mice or genetic modified mice models, we will explore the metastasis-regulating roles of lncRNAs expressed in stromal cells. By intervening the secretion and uptake of exosomal-lncRNAs, we will explore the metastasis-regulating roles and mechanisms of exosomal-lncRNAs in stromal cell-tumor cell interactions. We will then evaluate the co-expression of lncRNAs in clinical tumor samples and analyze its correlation with metastasis and prognosis of patients. By carrying out this sub-project, we will be able to identify a group of lncRNAs regulating activation and metastasis-promotion of stromal cells, collect evidences for exploring the possibility that lncRNA function as signal molecules, and provide novel targets for therapies targeting tumor micro-environment.