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Updated: Feb 23, 2026

Isolation and Culture Expansion of Tumor-specific Endothelial Cells
Published on: October 14, 2015
C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development
Yongfen Min1, Jingdong Li2,3, Peng Qu1
1Center for Cancer Research, National Cancer Institutes, Frederick, MD 21702, USA.
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.
Insights
The study identifies C/EBP-δ as a key regulator of myeloid-derived suppressor cells (MDSCs) and vascular endothelial growth factor receptor 2 (VEGFR2) in the tumor microenvironment. Targeting C/EBP-δ may offer a novel cancer therapy approach.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- The tumor microenvironment involves vascular endothelial cells and myeloid-derived suppressor cells (MDSCs).
- Targeting these components is a strategy for cancer therapy.
- A common mediator regulating both is yet to be fully elucidated.
Purpose of the Study:
- To identify a common mediator regulating both vascular endothelial cells and MDSCs in tumor development.
- To investigate the role of C/EBP-δ in tumor progression and its mechanisms of action.
Main Methods:
- Genetic deletion of C/EBP-δ in mice.
- Analysis of MDSC expansion and Gr-1+CD11b+ cell production.
- Assessment of tumor angiogenesis and growth.
- Investigation of C/EBP-δ expression and function in vascular endothelial cells, including VEGFR2 regulation.
- Chromatin immunoprecipitation to assess C/EBP-δ binding to the VEGFR2 promoter.
Main Results:
- C/EBP-δ is elevated in tumor-derived MDSCs and promotes their expansion under tumor conditions.
- Loss of C/EBP-δ reduces tumor angiogenesis and growth.
- C/EBP-δ regulates vascular endothelial cell motility, network formation, and sprouting.
- C/EBP-δ directly regulates VEGFR2 expression in endothelial cells via promoter recruitment.
Conclusions:
- C/EBP-δ is a crucial mediator promoting tumor development by regulating both MDSC expansion and VEGFR2 expression in endothelial cells.
- Targeting C/EBP-δ presents a potential dual-action strategy for cancer therapy.
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