FcγRIIB受体调控肿瘤转移的作用及机制研究

项目名称： FcγRIIB受体调控肿瘤转移的作用及机制研究

项目编号： No.81473230

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨勇

作者单位： 中国药科大学

项目金额： 80万元

中文摘要： 全世界癌症患者死亡约90%可归咎于肿瘤转移，阐明其发生过程及具体机制是目前亟待解决的重大科学问题。本课题组前期研究发现FcγRIIB-/-小鼠较WT小鼠更易发生黑色素瘤转移，具体机制未明。本项目主要研究内容包括：⑴FcγRIIB调控肿瘤转移起始细胞（MIC）形成的具体机制，重点研究其调控肿瘤细胞与骨髓造血干细胞HSC融合，以及融合细胞表观遗传修饰、重编程及干性（stemness）获得相关环节的分子机制。⑵FcγRIIB对循环肿瘤细胞及转移灶的调控机制，以FcγRIIB缺失所导致炎症微环境为出发点，研究肿瘤转移进展过程中循环肿瘤细胞干性调节及转移前Niche的形成机制。（3）应用激活型受体FcRγ-/-小鼠及临床样本验证上述研究结论，从分子、细胞、动物模型和临床病例等多个水平，阐明FcγRIIB在肿瘤转移发生发展各重要环节的确切调控机制，为研发预防和治疗肿瘤转移的新药提供理论依据和实验基础。

中文关键词： FcγRIIB受体；肿瘤转移；肿瘤微环境；黑色素瘤；肿瘤干细胞

英文摘要： Tumor metastasis is responsible for as much as 90% of cancer-associated mortality worldwide. However, Its process and molecular mechanism are poorly understood and it's of great importance to clarify them. Our previous work showed that metastasis of melanoma was much more severer in FcγRIIB-/- mice compared to wild type mice, yet the mechanism remains elusive. This project will focus on the following contents: ⑴ The concrete mechanism of FcγRIIB in regulating metastasis-initiating cells (MIC) formation. It will focus on the fusion process of tumor cells and hematopoietic stem cell(HSC) and the functional changes of the fusion hybrids which may acquire stemness after epigenetic regulation, such as reprogramming ,which finally formed MIC. ⑵ The roles of FcγRIIB in the progress of metastasis. FcγRIIB deficiency will result in inflammatory microenvironment, which affects the stemness of circulation tumor cell and formation of pre-metastasis niche. The mechanism of the process will be investigated. ⑶ Using activating FcγR receptor knock-out mice (FcRγ-/-) and clinical samples, we will clarify the regulatory role of FcγRIIB in the important processes during tumor metastasis on molecular ,cellular and animal levels, which will provide theoretical and experimental basis for research and development of new drugs preventing and treating tumor metastasis.

英文关键词： FcγRIIB;tumor metastasis;tumor microenvironment;melanoma;cancer stem cell