2. Academic Validation
  3. IL-17A-stimulated endothelial fatty acid β-oxidation promotes tumor angiogenesis

IL-17A-stimulated endothelial fatty acid β-oxidation promotes tumor angiogenesis

  • Life Sci. 2019 Jul 15;229:46-56. doi: 10.1016/j.lfs.2019.05.030.
Ruirui Wang 1,  Xiaohan Lou 1,  Guang Feng 2,  Jinfeng Chen 3,  Linyu Zhu 1,  Xiaomeng Liu 1,  Xiaohan Yao 1,  Pan Li 4,  Jiajia Wan 1,  Yi Zhang 5,  Chen Ni 6,  Zhihai Qin 7
Affiliations

Affiliations

  • 1 Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China.
  • 2 Department of Orthopedics, Zhengzhou Central Hospital, Zhengzhou, Henan Province 450052, China.
  • 3 Research Center for Clinical System Biology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China.
  • 4 Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China.
  • 5 Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China.
  • 6 Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China. Electronic address: [email protected].
  • 7 Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China; Key Laboratory of Protein and Peptide Pharmaceuticals, CAS-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing, 100000, China. Electronic address: [email protected].
PMID: 31085243 DOI: 10.1016/j.lfs.2019.05.030
Abstract

Aims: Tumor growth is an angiogenesis-dependent process that requires sustained new vessel growth. Interleukin-17 (IL-17A) is a key cytokine that modulates tumor progression. However, whether IL-17A affects the metabolism of endothelial cells is unknown.

Main methods: A xenograft model was established by implanting H460 (human lung Cancer cell line) cells transfected with IL-17A-expressing or control vector. The effects of IL-17A on sprouting and tube formation of human umbilical vein endothelial cells (HUVECs) were measured. After treatment with IL-17A, the proliferation and migration of HUVECs were examined. Liquid chromatography-mass spectrometry (LC-MS) and Seahorse were used to detect the effects of IL-17A on mitochondrial respiration and fatty acid β-oxidation (FAO) in HUVECs. Western blotting was used to examine signaling pathways.

Key findings: Herein, we found that IL-17A promoted H460 tumor growth and angiogenesis in vivo and in vitro. Moreover, IL-17A stimulated angiogenesis by enhancing FAO, increasing mitochondrial respiration of endothelial cells. The AMP-activated protein kinase (AMPK) signaling pathway was activated to promote FAO. Finally, IL-17A-induced angiogenesis was blocked when FAO was inhibited using etomoxir.

Significance: In summary, these results indicate that IL-17A stimulates angiogenesis by promoting FAO. Thus, our study might provide a new therapeutic target for angiogenic vascular disorders.

Keywords

AMPK; Angiogenesis; FAO; IL-17A; Mitochondrial respiration.

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