TNFSF15 facilitates the differentiation of CD11b^(+) myeloid cells into vascular pericytes in tumors  

作　　者：Xiangxiang Gu Yipan Zhu Cancan Zhao Yixin Cao Jingying Wang Qiangzhe Zhang Luyuan Li 

机构地区：[1]State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy,Nankai University,and Haihe Laboratory of Cell Ecosystem,Tianjin 300350,China

出　　处：《Cancer Biology & Medicine》2023年第11期869-884,共16页癌症生物学与医学（英文版）

基　　金：supported partly by the National Natural Science Foundation of China(Grant Nos.82073064 and 81874167 to LYL,and 82073233 to ZQZ);Haihe Laboratory of Cell Ecosystem Innovation Fund(Grant No.22HHXBSS00020 to LYL);Ministry of Education 111 Project(Grant No.B20016 to LYL)。

摘　　要：Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.

关 键 词：TNFSF15 myeloid cell NEOVASCULARIZATION CD11b^(+)cell PERICYTE 

分 类 号：R730[医药卫生—肿瘤]