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.

Oncotarget
|September 9, 2017
PubMed

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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