肿瘤细胞源性外泌体microRNAs诱导巨噬细胞极化重塑肿瘤转移微环境

Tumor invasion and metastasis depends not only on the genetic and epigenetic properties of tumor cell, and also on the effects from the phenotypic changes of stromal cells such like macrophage polarization in the microenvironment. As signal mediators, exosome microRNAs play an important role in remodeling process in tumor microenvironment by regulating the biological behaviors of tumor cells and stromal cells. However, little is known about the induction mechanism of the tumor cell derived exosome microRNAs on stromal cells. Targeting onto the regulation network consisting of tumor cell, exosome microRNAs, immune related signaling pathways, macrophage polarization, this project try to uncover the mechanism of tumor cell derived exosome microRNAs inducing macrophage polarization to remodel tumor microenvironment in regulation of tumor invasion and metastasis. Integrating with both basic mechanism studies and translational medicine in practice will enhance the research value and significance of the project.

肿瘤的侵袭、转移不仅取决于肿瘤细胞的遗传和表观遗传特性，同样也有赖于微环境中巨噬细胞极化等基质细胞表型变化的影响。外泌体microRNA通过调控微环境中肿瘤细胞和基质细胞的生物学行为，在肿瘤微环境的重塑过程中发挥了重要的中介信号作用。然而，肿瘤细胞来源的外泌体microRNA如何诱导调控基质细胞的研究甚少。本课题以肿瘤细胞-外泌体microRNA-免疫相关信号通路-巨噬细胞极化调控网络为靶向，探索肿瘤细胞源性外泌体microRNA如何通过诱导巨噬细胞极化重塑肿瘤微环境以调控肿瘤的侵袭转移。课题既结合肿瘤生物学机制的研究，同时将转化医学的理念贯穿于课题实施中，将对提升该课题的研究价值与意义提供保障。

肿瘤的侵袭、转移不仅取决于肿瘤细胞的遗传和表观遗传特性，同样也有赖于微环境中巨噬细胞极化等基质细胞表型变化的影响。外泌体通过调控微环境中肿瘤细胞和基质细胞的生物学行为，在肿瘤微环境的重塑过程中发挥了重要的中介信号作用。本课题从三个方面开展相关研究：肿瘤细胞外泌体miR-200c、miR-205调控乳腺癌细胞迁移与侵袭的实验研究；乳腺癌细胞外泌体诱导巨噬细胞极化的实验研究；肿瘤相关性巨噬细胞外泌体对乳腺癌细胞生物学行为的影响及其机制。以此分析外泌体以及外泌体microRNA重塑肿瘤微环境以调控乳腺癌转移的作用和内在机制进行了初步探索，发现肿瘤微环境中的肿瘤细胞之间及其与巨噬细胞之间均存在密切的依赖外泌体进行信号交流的方式，且这种信号交流可以影响乳腺癌的转移行为。课题研究既结合肿瘤生物学机制探索，同时将转化医学的理念贯穿于课题实施中，为以外泌体为靶向的乳腺癌临床治疗提供了理论基础。