三阴性乳腺癌分泌M-CSF的机制研究及M-CSF对三阴性乳腺癌转移的促进作用

批准号:
82002820
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
路晓庆
依托单位:
学科分类:
肿瘤免疫治疗
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
路晓庆
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中文摘要
三阴性乳腺癌(triple negative breast cancer, TNBC)是预后最差的一种乳腺癌分型,本课题组前期发现TNBC具有显著招募巨噬细胞的能力,并证明这种差异是由TNBC分泌的巨噬细胞集落刺激因子(M-CSF)所致;此外还发现巨噬细胞胞内的RhoA蛋白发生由胞浆移位到胞核的核移位现象。因此我们假设TNBC通过分泌M-CSF来调节巨噬细胞内RhoA蛋白的细胞定位,改变巨噬细胞的迁移能力从而招募巨噬细胞进入肿瘤周围环境,最终促进TNBC转移。本项目将深入探究TNBC分泌M-CSF的机制,建立类器官与巨噬细胞共培养体系以模拟乳腺癌细胞与微环境的多向作用,观察M-CSF对TNBC转移的影响,评估M-CSF作为预测患者预后情况标志物的可能性及M-CSF抗体治疗TNBC的疗效,最终为进一步理解TNBC发展机制以及发展新的治疗策略提供方向。
英文摘要
Triple negative breast cancer (TNBC) is the type of breast cancer with the worst prognosis. In the early stage, TNBC was found to have a significant ability to recruit macrophages, and it was proved that this difference was caused by the macrophage-colony stimulating factor (M-CSF) secreted by TNBC.In addition, RhoA protein in macrophages underwent nuclear translocation from cytoplasm to nucleus.Therefore, we hypothesized that TNBC could regulate the cellular localization of RhoA protein in macrophages by secreting M-CSF, and change the migration ability of macrophages so as to recruit macrophages into the surrounding environment of the tumor and ultimately promote TNBC metastasis.This project will continue to explore the mechanism by which TNBC secretes M-CSF, establish a co-culture system of organoids and macrophages to simulate the multidirectional effect of breast cancer cells and microenvironment, and observe the effect of M-CSF on TNBC metastasis.Evaluating the possibility of M-CSF as a predictor of prognosis and the efficacy of M-CSF antibody in the treatment of TNBC. Provide directions for further understanding of the development mechanism of TNBC and the development of new treatment strategies.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription
EGFR 信号传导促进质膜蛋白 TSPAN8 的核转位,通过 STAT3 介导的转录增强肿瘤进展
DOI:10.1038/s41422-022-00628-8
发表时间:2022-02-23
期刊:CELL RESEARCH
影响因子:44.1
作者:Lu, Xiaoqing;An, Liwei;Wang, Hongxia
通讯作者:Wang, Hongxia
DOI:10.3389/fonc.2022.940314
发表时间:2022
期刊:FRONTIERS IN ONCOLOGY
影响因子:4.7
作者:Liu, Xiangrong;Papukashvili, Dimitri;Wang, Zhixiang;Liu, Yan;Chen, Xiaoxia;Li, Jianrong;Li, Zhiyuan;Hu, Linjie;Li, Zheng;Rcheulishvili, Nino;Lu, Xiaoqing;Ma, Jinfeng
通讯作者:Ma, Jinfeng
DOI:10.1038/s41419-023-06108-0
发表时间:2023-09-01
期刊:CELL DEATH & DISEASE
影响因子:9
作者:Zhang, Lichao;Lu, Xiaoqing;Xu, Yuanzhi;La, Xiaoqin;Tian, Jinmiao;Li, Aiping;Li, Hanqing;Wu, Changxin;Xi, Yanfeng;Song, Guisheng;Zhou, Zhaocai;Bai, Wenqi;An, Liwei;Li, Zhuoyu
通讯作者:Li, Zhuoyu
国内基金
海外基金
