钙离子信号相关microRNA调控肿瘤微环境下骨髓间充质干细胞分化机制及其致瘤作用研究

Nasopharyngeal carcinoma is commonly seen in south of China. The metastasis of nasopharyngeal carcinoma affects survival rates. Tumor microenvironment contributes to the development of nasopharyngeal carcinoma. Bone marrow derived mesenchymal stem cells are capable of differentiating and homing to tumor sites, making them the main component of tumor microenvironment. Our previous work showed that mesenchymal stem cells in tumor microenvironment differentiated into CD45+/CD34+/CD11b+ subpopulation which displayed characteristics of macrophaege. This population of cells promoted invasion and metastasis of nasopharyngeal carcinoma cells and bone destruction properties by secreting nitric oxide. Calcium channel blocking obviously increased the rate of differentiated CD45+/CD34+/CD11b+ subpopulation. microRNA expression profile showed that the differentiation of mesenchymal stem cells in tumor microenvironment is regulated by calcium signaling. The aim of this proposal is to investigate the roles of CD45+/CD34+/CD11b+ subpopulation of mesenchymal stem cells in the growth and invasion of nasopharyngeal carcinoma and related mechanisms. The roles of calcium signaling associated microRNA in the differentiation through regulating calcium oscillation and calcium related kinase will be investigated. The completion of the proposal will partly elucidate the contribution of differentiation of mesenchymal stem cells to the malignant behaviour of nasopharyngeal carcinoma.

鼻咽癌是我国南方高发肿瘤，其晚期转移极大影响患者的生存率。肿瘤微环境对鼻咽癌发生发展发挥重要作用。骨髓来源间充质干细胞具有多向分化潜能和向肿瘤定向迁移的能力，是肿瘤微环境重要组成成分。我们前期研究表明，肿瘤微环境下间充质干细胞分化出具有巨噬细胞表型的CD45+/CD34+/CD11b+细胞，通过分泌一氧化氮，促进鼻咽癌细胞侵袭转移以及骨质破坏能力。钙离子通道阻滞明显增加CD45+/CD34+/CD11b+细胞的比例。microRNA表达谱显示在肿瘤微环境下间充质干细胞分化受到钙离子信号的影响。本项目拟深入研究CD45+/CD34+/CD11b+间充质干细胞亚群对鼻咽癌细胞生长以及侵袭能力的影响及其相关机制，并探讨钙离子信号相关的microRNA通过调控钙振荡和钙离子相关激酶影响肿瘤微环境下间充质干细胞分化潜能的作用。该项目的完成将部分阐明骨髓间充质干细胞的分化对于鼻咽癌细胞恶性表型的影响。

鼻咽癌晚期转移极大影响患者的生存率。肿瘤微环境对鼻咽癌发生发展发挥重要作用。骨髓来源间充质干细胞具有多向分化潜能和向肿瘤定向迁移的能力，是肿瘤.微环境重要组成成分。我们前期研究表明，肿瘤微环境下间充质干细胞分化出具有巨噬细胞表型的CD45+/CD34+/CD11b+细胞，通过分泌一氧化氮，促进鼻咽癌细胞侵袭转移以及骨质破坏能力。钙离子通道阻滞明显增加CD45+/CD34+/CD11b+细胞的比例。microRNA表达谱显示在肿瘤微环境下间充质干细胞分化受到钙离子信号的影响。因此，我们拟深入研究CD45+/CD34+/CD11b+间充质干细胞亚群对鼻咽癌细胞生长以及侵袭能力的影响及其相关机制，并探讨钙离子信号相关的microRNA通过调控钙振荡和钙离子相关激酶影响肿瘤微环境下间充质干细胞分化潜能的作用。该项目的完成将部分阐明骨髓间充质干细胞的分化对于鼻咽癌细胞恶性表型的影响。