细胞外基质蛋白reelin对多发性骨髓瘤增殖和分化的影响及其机制

项目名称： 细胞外基质蛋白reelin对多发性骨髓瘤增殖和分化的影响及其机制

项目编号： No.81670192

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 路瑾

作者单位： 北京大学

项目金额： 25万元

中文摘要： 前期工作中我们发现调节神经元迁移的关键分子reelin在多发性骨髓瘤患者的瘤细胞中表达，且表达水平与患者无进展生存期和总生存期呈显著负相关。Reelin通过活化整合素β1及其下游的FAK/Src/Syk/STAT3和Akt通路促进骨髓瘤细胞对纤连蛋白的粘附和存活，以及粘附介导的耐药。进一步的研究发现reelin还能促进骨髓瘤细胞的增殖以及干细胞相关分子的表达。本项目将深入探讨reelin对骨髓瘤细胞增殖和分化的调控作用及其分子机制，明确reelin能否作为指导骨髓瘤治疗的生物标志物。这些研究结果将促进对骨髓瘤发生和发展机理的深入理解，为未来的靶向治疗提供可能。

中文关键词： 多发性骨髓瘤；细胞外基质蛋白；增殖；分化

英文摘要： Reelin is an extracellular matrix glycoprotein that plays a pivotal role in the regulation of cell migration and positioning control. Little is known of the role of reelin on multiple myeloma. We found expression of reelin in primary myeloma cells in the bone marrow. The expression level is negatively correlated with progression-free survival and overall survival in multiple myeloma patients. Reelin was also found promoting the adhesion and survival of myeloma cells via activation of integrin beta1 and FAK/Src/Syk/STAT3 and Akt pathways. We further found that reelin promoted the proliferation of myeloma cells and enhanced the expression of stemness markers. Thus, the current project will investigate the mechanisms underlying the role of reelin on myeloma cell proliferation and differentiation. The results from this research will facilitate our understanding of the development and progression of myeloma and will provide new clues and evidence for better diagnosis and prognosis, and more therapeutic potentials.

英文关键词： multiple myeloma;extracellular matrix protein;proliferation;differentiation