Serum interleukin (IL)‑17A level is associated with higher microvessel density and poor prognosis in liver cancer. However, the specific mechanism underlying the role of IL‑17A in liver cancer remains controversial. In the present study, the effect of IL‑17A on liver cancer cells was examined. IL‑17A had no evident impact on vascular endothelial growth factor A (VEGFA) production in HepG2 and Huh7.5 cells as determined by reverse transcription‑quantitative PCR and ELISA, but it did stimulate angiogenic CXC chemokine secretion, including chemokine (C‑X‑C motif) ligand 1 (CXCL1), CXCL2, CXCL3, CXCL5, CXCL6 and CXCL8 in Huh7.5 cells and CXCL2 in HepG2 cells. In addition, the production of angiostatic... More
Serum interleukin (IL)‑17A level is associated with higher microvessel density and poor prognosis in liver cancer. However, the specific mechanism underlying the role of IL‑17A in liver cancer remains controversial. In the present study, the effect of IL‑17A on liver cancer cells was examined. IL‑17A had no evident impact on vascular endothelial growth factor A (VEGFA) production in HepG2 and Huh7.5 cells as determined by reverse transcription‑quantitative PCR and ELISA, but it did stimulate angiogenic CXC chemokine secretion, including chemokine (C‑X‑C motif) ligand 1 (CXCL1), CXCL2, CXCL3, CXCL5, CXCL6 and CXCL8 in Huh7.5 cells and CXCL2 in HepG2 cells. In addition, the production of angiostatic chemokines such as CXCL10 was not affected. The supernatant of Huh7.5‑IL17A cells promoted endothelial cell chemotaxis, which was attenuated by the C‑X‑C chemokine receptor type 2 (CXCR2) inhibitor SB225002. Although there was no role of IL‑17A in promoting in vitro cell proliferation, IL‑17A markedly increased the tumor growth of Huh7.5 cells in both subcutaneous and orthotopic xenograft models with increased vascularization. Taken together, these results demonstrated that IL‑17A may stimulate chemokine‑induced angiogenesis and promote tumor progression, independent of VEGF signaling. The CXCL‑CXCR2 axis may be a novel target for the anti‑angiogenesis treatment of liver cancer.
