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Interleukin-17F suppressed colon cancer by enhancing caspase 4 mediated pyroptosis of endothelial cells

Ying Zhou1, Mei Yang1, Rishun Fu1

  • 1TaiKang Medical School (School of Basic Medicine Sciences), Wuhan University, Donghu Road, No. 185, Wuhan, 430071, China.

Scientific Reports
|August 7, 2024
PubMed

Insights

Interleukin-17F (IL-17F) suppresses colon cancer growth by inhibiting angiogenesis and promoting immune cell recruitment. This cytokine enhances Caspase 4/GSDMD signaling, leading to endothelial cell pyroptosis and a modulated tumor microenvironment.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Colon cancer treatment benefits from combining anti-angiogenic therapy and immunotherapy.
  • Interleukin-17F (IL-17F), a cytokine in colonic epithelial cells, shows potential in inhibiting angiogenesis.
  • Understanding IL-17F's role in the colon cancer microenvironment is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of IL-17F in the colon cancer microenvironment.
  • To elucidate the underlying mechanisms of IL-17F's anti-tumor effects.
  • To explore IL-17F as a potential therapeutic target for colon cancer.

Main Methods:

  • Established a mouse colon carcinoma cell line (CT26) overexpressing IL-17F for subcutaneous transplantation.
  • Analyzed colon tumors in IL-17F knockout and wild-type mice.
  • Performed in vitro experiments on endothelial cells (EOMA) treated with IL-17F.
  • Conducted transcriptome analysis and molecular validation of key signaling pathways.

Main Results:

  • IL-17F suppressed colon tumor growth in vivo, accompanied by inhibited angiogenesis and increased recruitment of CCR6+ immune cells.
  • IL-17F inhibited endothelial cell tube formation, growth, and migration in vitro.
  • IL-17F treatment upregulated Caspase 4 expression in endothelial cells, activating the Caspase 4/GSDMD pathway and promoting endothelial cell pyroptosis.
  • IL-17F knockout tumors showed decreased Caspase 4/GSDMD signaling.

Conclusions:

  • IL-17F modulates the colon tumor microenvironment by inhibiting angiogenesis and inducing endothelial cell pyroptosis.
  • IL-17F demonstrates significant potential as a therapeutic target for colon cancer, particularly in combination strategies.
  • The IL-17F/Caspase 4/GSDMD axis represents a novel signaling pathway influencing colon tumor progression.
Keywords:
AngiogenesisCaspase 4Colon cancerIL-17FPyroptosis

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