研究表明肿瘤干细胞是参与乳腺癌化疗耐药的重要机制，其生物学特性受肿瘤微环境间质细胞的调控。我们前期研究发现肿瘤微环境中数目最多的炎症细胞肿瘤相关巨噬细胞（TAMs）通过CCL18促进肿瘤细胞迁移。但TAMs是否调控肿瘤干细胞的生物学特性和化疗耐药目前尚不清楚。最近我们又发现TAM的激活与肿瘤细胞上皮-间质转化（EMT）形成正反馈环路，维持肿瘤细胞EMT表型，并与肿瘤干细胞生成密切相关。在此基础上，本课题将通过TAMs与肿瘤细胞体外共培养模型、人源化小鼠肿瘤模型和术前化疗病人标本的分析，研究TAMs诱导肿瘤干细胞富集和化疗耐药的生物学现象，并进一步探索其潜在的分子机制。本研究有助于进一步揭示非可控性炎症微环境对肿瘤细胞可塑性调控的分子网络，为针对相关节点分子发展新型乳腺癌靶向治疗提供理论依据。

Studies have shown that cancer stem cells(CSCs) played an important role in chemo-resistance of breast cancer and its biological characteristics were regulated by the strmal cells in the tumor microenvironment. Our previous study found that tumor-associated macrophages (TAMs)are the moust abundant inflammatory cells in breast cancer microenvironment and it could promote the metastasis of breast cancer via the secretion of CCL18. However, whether TAMs regulated the biological characteristics of CSCs is still unclear. Recently, we also found that there is a positive feedback loop between the activation of TAMs and the epithelial - mesenchymal transition (EMT) of breast cancer cells. The exist of this loop maintains the EMT phenotype of tumor cells, and is significantly correlated to the generation of cancer stem cells. Based on these, this subject will study whether TAMs enrich CSCs and induce chemo-resistance in breast cancer and further explore the underlying molecular mechanisms. This study will helps us to reveal the molecular regulation network of tumor cells plasticity regulated by the uncontrolled inflammatory microenvironment and provides a theoretical basis for the development of new molecule targets for breast cancer targeted therapy.