机构：[1]Center for Cancer Research, National Cancer Institutes, Frederick, MD 21702, USA.[2]Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637007, Sichuan, China.[3]Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute, North Sichuan Medical College, Nanchong 637007, Sichuan, China.
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development. It suggests a specific role of C/EBP-δ in emergency myelopoiesis under tumor conditions. Consistent with the pro tumor functions of MDSCs, loss of C/EBP-δ resulted in reduced tumor angiogenesis and tumor growth. Moreover, we found expression of C/EBP-δ in vascular endothelial cells. C/EBP-δ regulated cell motility, endothelial network formation and vascular sprouting. Notably, inactivation of C/EBP-δ in endothelial cells specifically inhibited the expression of VEGFR2 but not VEGFR1. Ectopic expression of C/EBP-δ increased and knockdown of the gene decreased VEGFR2 expression. C/EBP-δ is recruited to the promoter region of VEGFR2, indicative of transcriptional regulation. Collectively, this study has identified a positive mediator in C/EBP-δ, which regulates tumor induced MDSC expansion and VEGFR2 expression in endothelium. Considering the importance of MDSCs and endothelial cells in tumor progression, targeting C/EBP-δ may provide an interesting means for cancer therapy, killing two birds with one stone.
基金：
This work is supported by the Intramural Research
Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Center for Cancer Research, National Cancer Institutes, Frederick, MD 21702, USA.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Min Yongfen,Li Jingdong,Qu Peng,et al.C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development.[J].Oncotarget.2017,8(31):50582-50593.doi:10.18632/oncotarget.16410.
APA：
Min Yongfen,Li Jingdong,Qu Peng&Lin P Charles.(2017).C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development..Oncotarget,8,(31)
MLA：
Min Yongfen,et al."C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development.".Oncotarget 8..31(2017):50582-50593
