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P. Charles Lin

National Cancer Institute, USA

Title: C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development

Biography

Biography: P. Charles Lin

Abstract

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-d that regulates both components and aids in tumor development. C/EBP-d is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-d 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-d in emergency myelopoiesis under tumor conditions. Consistent with the pro tumor functions of MDSCs, loss of C/EBP-d resulted in reduced tumor angiogenesis and tumor growth. Moreover, we found expression of C/EBP-d in vascular endothelial cells. C/EBP-d regulated cell motility, endothelial network formation and vascular sprouting. Notably, inactivation of C/EBP-d in endothelial cells specifically inhibited the expression of VEGFR2 but not VEGFR1. Ectopic expression of C/EBP-d increased and knockdown of the gene decreased VEGFR2 expression. C/EBP-d is recruited to the promoter region of VEGFR2, indicative of transcriptional regulation. Collectively, this study has identified a positive mediator in C/EBP-d, 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-d may provide an interesting means for cancer therapy, killing two birds with one stone.