膀胱癌细胞如何定向进入淋巴结发生淋巴转移的机制尚不清楚。我们的前期研究发现，膀胱癌细胞异常表达归巢受体CD62L，可能使其模拟淋巴细胞归巢促进淋巴结转移；而CD62L表达上调的机制可能是肿瘤相关成纤维细胞（CAFs）通过外泌体转运非编码RNA BLACAT3导致。本课题拟进一步：应用共培养模型、淋巴归巢及转移动物模型等进一步证实CAFs通过外泌体转运BLACAT3分子在膀胱癌细胞向淋巴结“归巢”运动和淋巴转移中的关键作用；阐明BLACAT3通过SMARCAD1调控CD62L启动子转录活性的分子机制。本项目紧紧围绕“CAFs通过外泌体转运BLACAT3至膀胱癌细胞，形成BLACAT3-SMARCAD1复合物进而激活CD62L表达促进淋巴转移”这一科学假说，从BLACAT3的全新调控机制入手，揭示其促进膀胱癌淋巴转移的本质，为开发膀胱癌治疗新靶点提供原创性的科学依据。

The mechanism by which bladder cancer cells are directed into lymph nodes and subsequently causing lymphatic metastasis is still unclear. Our previous study found that abnormal expression of the homing receptor CD62L in bladder cancer cells may promote lymph node metastasis by inducing the homing behavior of cancer cells. Furthermore, the up-regulation of CD62L may be due to the transport of non-coding RNA BLACAT3 from tumor-associated fibroblasts (CAFs) to bladder cancer cells through exosomes. This project focuses on the scientific hypothesis that “CAFs transport BLACAT3 to bladder cancer cells through exosomes, forming BLACAT3-SMARCAD1 complex and activates CD62L expression to promote lymphatic metastasis”. We will elucidate a novel regulation mechanism BLACAT3 in promoting of lymph node metastasis of bladder cancer. The project will provide original scientific basis for the development of new targets for the treatment of bladder cancer.