Nampt在肿瘤相关巨噬细胞介导的乳腺癌转移中的作用及机制研究

Distant metastasis is the main cause of death in breast cancer patients, so it is crucial to clarify the mechanism of breast cancer metastasis for reducing mortality and improving current treatments. Studies have shown that tumor-associated macrophages (TAMs) are involved in the process of tumor invasion and metastasis as an important component in the tumor inflammatory microenvironment, which are the important link between inflammation and tumor. As pro-inflammatory cytokine, Nicotinamide phosphoribosyl transferase (Nampt) not only regulates the survival and promotes the inflammation of macrophages, but also participates the occurrence and development of breast cancer closely. Preliminary results indicated that Nampt can enhance the inflammation of tumor cells, regulate the inflammatory microenvironment of tumor and Nampt overexpression can significantly promote the proliferation and metastasis of breast cancer cells, but the exact mechanism of Nampt in inflammatory microenvironment-induced metastasis of breast cancer is still unknown. This project will focus on the important pathological process of inflammation-induced tumor, systematically investigate the regulation by Nampt on phenotypic differentiation of TAMs and clarify the role of Nampt in TAMs-mediated metastasis of breast cancer with multidisciplinary technical means at different levels. The activation of signal transduction pathways that connects inflammation with tumor will be further detected to investigate the molecular mechanisms of Nampt in TAMs mediated breast cancer metastasis. These findings will afford experimental and theoretical basis for Nampt as a new target in clinical diagnosis and treatment of breast cancer.

远处转移是乳腺癌患者死亡的主要原因。目前认为肿瘤相关巨噬细胞(TAMs)具有促进肿瘤侵袭和转移的作用，是连接炎症与肿瘤的重要纽带。研究表明烟酰胺磷酸核糖转移酶(Nampt)作为促炎细胞因子不仅可以调控巨噬细胞的生存和促炎症活力，而且与乳腺癌的发生发展密切相关。前期工作证明Nampt可以通过促进肿瘤细胞的炎症反应进而参与肿瘤炎性微环境的调控，并且 Nampt过表达能显著促进乳腺癌细胞的转移，但Nampt在炎性微环境介导的乳腺癌转移中的作用及机制不详。本项目将围绕炎症诱导肿瘤这一重要病理过程，综合运用多学科的技术手段，多角度、多层面、系统地研究Nampt对TAMs 表型和功能的调控作用，阐明其在TAMs介导的乳腺癌转移中的作用，在此基础上通过检测炎症－肿瘤偶联信号通路的活化情况，探讨Nampt在TAMs介导的乳腺癌转移中的分子机制，为Nampt作为乳腺癌临床诊治的新靶点提供实验基础和理论依据。