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

15Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

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-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.

Cite

CITATION STYLE

APA

Min, Y., Li, J., Qu, P., & Lin, P. C. (2017). C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development. Oncotarget, 8(31), 50582–50593. https://doi.org/10.18632/oncotarget.16410

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free