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

Life sciences (2019-05-16)
Ruirui Wang, Xiaohan Lou, Guang Feng, Jinfeng Chen, Linyu Zhu, Xiaomeng Liu, Xiaohan Yao, Pan Li, Jiajia Wan, Yi Zhang, Chen Ni, Zhihai Qin
ABSTRACT

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. 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. 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. 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.