膀胱肿瘤在我国具有发病率和复发率均较高的特点，目前促进其进展的机制仍未完全清楚。内皮细胞作为脉管系统的基本组成之一及肿瘤微环境的重要组成成分，在肿瘤生长过程中起重要作用，而其对膀胱肿瘤细胞侵袭迁移作用的研究非常少。本课题前期临床标本研究证实了内皮细胞（EC）与膀胱肿瘤的恶性行为相关。同时通过共培养膀胱肿瘤细胞与内皮细胞模拟肿瘤微环境，体外发现内皮细胞与肿瘤细胞的相互作用通过血管生成之外途径促进膀胱肿瘤细胞增殖、侵袭及迁移，并与CXC趋化因子及其受体表达升高以及NF-κB 通路激活相关。下一步我们拟探讨NF-κB 介导的CXC趋化因子在内皮细胞-膀胱肿瘤相互作用促进膀胱肿瘤细胞侵袭迁移的作用及其机制，同时结合蛋白质芯片分析和cDNA基因芯片技术对NF-κB 激活上游通路的研究，整体阐述此作用体系中的信号通路和作用机制,为下一步从分子水平靶向干预膀胱肿瘤细胞侵袭及迁移打下良好的基础。

Bladder tumor is characterized with high morbidity and recurrence in pathology. However, the molecular mechanisms that promote tumor progression are still poorly understood. Endothelial cell (EC), which is regarded as main component of blood vessels and tumor microenvironment, plays an important role in tumor growth, but the study about EC ’s effect on bladder tumor invasion and migration is much rare. Our preliminary data based on clinical specimens indicated that EC was associated with the malignant behavior of bladder cancer. Additionally, when bladder tumor cell was co-cultured with EC cell, which was regarded to mimic the microenvironment of tumor niche, we found that the interactions of endothelial cells and tumor cells in vitro could enhance tumor cell progression via angiogenesis-independent manner. That could be induced by NF-κB mediated CXC /CXC receptor expression. Thus, this proposed project will further investigate the role of NF-κB mediated CXC chemokines in the interaction of endothelial cells and tumor cells to promote bladder tumor cell progression and its mechanism. Along with upstream signaling screening of NF-κB signaling activation by cDNA microarray and protein chip, the signaling and molecular mechanisms in the interaction of endothelial cells and tumor cells will be expounded systematically, which might benefit targeted therapy on bladder tumor progression in the future.