项目名称： 诱导多能性干细胞源性巨噬细胞极化状态调控上皮性卵巢癌转移能力机制的研究

项目编号： No.81502247

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 黄宇婷

作者单位： 天津医科大学

项目金额： 18万元

中文摘要： 卵巢癌多因复发转移和化疗耐药导致治疗效果不理想，死亡率居妇科肿瘤之首。肿瘤相关巨噬细胞（TAM）为M2d型巨噬细胞，在卵巢癌转移中发挥重要作用。巨噬细胞基因组稳定性高，是卵巢癌治疗的理想靶点。由于TAM在改变微环境后表型和功能均发生变化，目前缺少研究TAM与肿瘤细胞相互作用的理想体系。诱导多能性干细胞（iPSCs）是近几年再生医学和细胞治疗研究的重点和热点。我们前期工作已成功建立了人iPSCs定向向单核巨噬细胞方向分化体系，以获得大量高纯度表型稳定的M1、M2型巨噬细胞。本课题将运用该体系并结合tet-on蛋白表达系统阐明对上皮性卵巢癌转移的调控机制，包括对上皮间质转化和失巢凋亡等方面的作用，以揭示iPSCs来源巨噬细胞极化状态抑制卵巢癌转移的调控作用与机理，本课题的成功实施将有助于阐明巨噬细胞在卵巢癌转移中的作用和意义，为探索使用人iPSCs来源巨噬细胞进行细胞治疗的可能性提供实验基础。

中文关键词： 卵巢肿瘤；巨噬细胞；诱导多能性干细胞；转移；上皮间质转化

英文摘要： Metastasis and resistance to chemotherapy often lead to the unsuccessfulness of the treatment of ovarian cancer, the first killer in gynecological tumors. Tumor-associated macrophages (TAM), also known as M2d macrophages, play an important role in ovarian cancer metastasis. With the high stability in genome, TAM has been highlighted as an ideal target for ovarian cancer. But, both phenotype and functions change along with the microenvironment, making it difficult to study the interaction between tumor cells and TAM. Regenerative medicine and cell therapy research has been focused on induced pluripotent stem cells (iPSCs). In our previous study, we successfully established a feeder-free differentiation systems through which iPSCs would be directed differentiated into monocytes and then high-purity phenotypically stable M1, M2 macrophages. In the current study we will use this differentiation system to study the mechanisms of macrophage polarization state regulating metastasis in epithelial ovarian cancer, including the impact on epithelial-mesenchymal transition, anoikis, etc. And then we will further use the tet-on system to turn off the expression of M-CSF receptor when differentiating into macrophages, to push macrophage polarization into M1 direction and study whether metastasis in ovarian cancer can be inhibited. The successful implementation of this project will help to clarify the role and significance of macrophages in ovarian cancer metastasis, and provide some experimental evidence for the possibility of using human iPSCs source macrophage in cell therapy.

英文关键词： ovarian cancer;macrophage;induced pluripotent stem cell;metastasis;epithelial-mesenchymal transition