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Phosphatidylserine released from apoptotic cells in tumor induces m2-like macrophage polarization through the PSR-STAT3-JmJD3 axis

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Cancer Communications 2022年第3期42卷 205-222页

作者： Xiao Liang min Luo Bin Shao Jing-Yun Yang An Tong Rui-Bo Wang Yan-Tong Liu Ren Jun Ting Liu Tao Yi Xia Zhao Yu-Quan Wei Xia-Wei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041P.R.China Department of Gynecology and Obstetrics Key Laboratory of Obstetrics&Gynecologic and Pediatric Diseases and Birth Defects of Ministry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041P.R.China

Background:Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic *** cells often undergo spontaneous apoptotic cell death in tumor microen-vironment,these apoptotic cells are histologically co-localized with immunosup-pressive ***,the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully *** this study,we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways ***:Apoptotic cells and macrophages in tumors were detected by immunohistochemical *** analysis was performed with Giemsa *** generated from apoptotic cells were detected by liq-uid chromatography-mass ***-containing lipo-somes were prepared to mimic apoptotic *** expression of protein was determined by real-time PCR,immunohistochemistry enzyme-linked immunosorbent assay and Western *** malignant ascites and subcu-taneous tumor models were designed for in vivo *** mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic ***:The location and the number of apoptotic cells were correlated with that of macrophages in several types of ***,a lipid molecule generated in apoptotic cells,induced polarization and accumulation of m2-like macrophages in vivo and in ***,sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcuta-neous tumor *** analyses suggested that phosphoserine induced a m2-like phenotype in macrophages,which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4(TIm4)and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3(JmJD3).Adminis-tration of

关键词： phosphatidylserine tumor cell apoptosis m2-like macrophage polarization JmJD3 STAT3

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