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

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.