膜蛋白FCGR2B调控骨肉瘤肺转移及其机制研究

骨肉瘤肺转移的预后差，而转移性骨肉瘤干细胞为肺转移的根源，因此，抑制该亚群细胞是阻断肺转移进程的关键。我们已证实NF-κB信号促进骨肉瘤肺转移。前期生物信息学分析发现FCGR2B在肺转移患者低表达，且功能机制学研究揭示其激活NF-κB信号通路，上调CD117+Stro-1+转移性骨肉瘤干细胞比例及促进骨肉瘤细胞迁移和侵袭，据此我们提出假设：在骨肉瘤细胞恶性转化的进程中，FCGR2B逐渐失活，可能通过激活NF-κB信号通路，活化转移性骨肉瘤干细胞，释放大量MMP9和c-FLIP等促转移因子，最终促进肺转移。血浆FCGR2B有助于肺转移的早期监测，抑制FCGR2B/NF-κB信号可抑制骨肉瘤转移性干细胞，有望阻断肺转移进程。本项目拟在前期基础上通过慢病毒系统调控、流式细胞技术、免疫共沉淀、质谱分析及体内成像等方法，从原代细胞、基因小鼠到临床标本深入探索FCGR2B调控肺转移的机制及其临床意义

The prognosis is poor in Osteosarcoma patients with lung metastasis and metastatic cancer stem cells are the sources of metastasis. Therefore, it’s vital to target these metastatic cancer stem cells to stop the process of metastasis. We have found that NF-κB signaling promote osteosarcoma metastasis. We previously revealed that lower expression level of FCGR2B in advanced patients. Our hypothesis is that FCGR2B activates the NF-KB signaling, promote activation of metastatic cancer stem cells, which eventually promotes lung metastasis. We plan to father study the mechanism behind the regulation of FCGR2B on osteosarcoma metastasis and also its potential clinical meanings.