PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway

作     者：Rui Zhang Mengxue Dong Juchuanli Tu Fengkai Li Qiaodan Deng Jiahui Xu Xueyan He Jiajun Ding Jie Xia Dandan Sheng Zhaoxia Chang Wei Ma Haonan Dong Yi Zhang Lixing Zhang Lu Zhang Suling Liu Rui Zhang;Mengxue Dong;Juchuanli Tu;Fengkai Li;Qiaodan Deng;Jiahui Xu;Xueyan He;Jiajun Ding;Jie Xia;Dandan Sheng;Zhaoxia Chang;Wei Ma;Haonan Dong;Yi Zhang;Lixing Zhang;Lu Zhang;Suling Liu

作者机构：Fudan University Shanghai Cancer Center&Institutes of Biomedical SciencesState Key Laboratory of Genetic EngineeringCancer InstitutesKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Breast SurgeryObstetrics and Gynecology Hospital of Fudan UniversityShanghaiChina Department of Breast and Thyroid SurgerySouthwest Hospitalthe First Affiliated Hospital of the Army Military Medical UniversityChongqing 400038China Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2023年第8卷第4期

页      面：1828-1841页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The National Key Research and Development Program of China(2020YFA0112300) National Natural Science Foundation of China(82230103,81930075,82203399,82073267) “Ten Thousand Plan”-National High-Level Talents Special Support Plan(WR-YK5202101) Program for Outstanding Leading Talents in Shanghai Program for Outstanding Medical Academic Leader in Shanghai(2019LJ04) Program of Shanghai Academic/Technology Research Leader(20XD1400700) The innovative research team of high-level local university in Shanghai 

主　　题：CCL20 CXCR2 breast 

摘      要：Our previous studies have showed that C-C motif chemokine ligand 20(CCL20)advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell(BCSC)***,it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment(TME).Here,we observed that polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft ***,CCL20 activated the differentiation of granulocyte-monocyte progenitors(GMPs)via its receptor C-C motif chemokine receptor 6(CCR6)leading to the PMN-MDSC ***-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors(CCL20-modulated PMN-MDSCs)secreted amounts of C-X-C motif chemokine ligand 2(CXCL2)and increased ALDH+BCSCs via activating CXCR2/NOTCH1/HEY1 signaling ***,C-X-C motif chemokine receptor 2(CXCR2)antagonist SB225002 enhanced the docetaxel(DTX)effects on tumor growth by decreasing BCSCs in CCL20high-expressing *** findings elucidated how CCL20 modulated the TME to promote cancer development,indicating a new therapeutic strategy by interfering with the interaction between PMN-MDSCs and BCSCs in breast cancer,especially in CCL20high-expressing breast cancer.