Panoply™ Human IL17A Over-expressing Stable Cell Line

Elevated serum levels of interleukin-17A (IL-17A) are associated with high microvessel density and poor prognosis in patients with liver cancer. However, the specific mechanisms by which IL-17A functions in liver cancer remain controversial. Here, researchers investigated the effects of IL-17A on liver cancer cells. RT-qPCR and ELISA analyses revealed that IL-17A did not significantly affect the production of vascular endothelial growth factor A (VEGFA) in HepG2 and Huh7.5 cells; however, it stimulated the secretion of pro-angiogenic CXC chemokines-specifically CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL8 in Huh7.5 cells, and CXCL2 in HepG2 cells. In contrast, the production of anti-angiogenic chemokines, such as CXCL10, remained unaffected. Supernatants from Huh7.5-IL17A cells promoted endothelial cell chemotaxis, an effect that was attenuated by the CXCR2 inhibitor SB225002. Although IL-17A did not promote cell proliferation in vitro, it significantly enhanced tumor growth and angiogenesis in Huh7.5 cells within both subcutaneous and orthotopic xenograft models. Collectively, these results suggest that IL-17A may promote tumor progression by stimulating chemokine-mediated angiogenesis, a process independent of the VEGF signaling pathway.

Here, the researchers investigated whether IL-17A might upregulate VEGFA expression in hepatocellular carcinoma cells, thereby promoting cell proliferation and angiogenesis. Notably, the results showed that VEGFA expression levels remained unchanged in IL-17A-overexpressing cells across all tested cell lines (Figure 1A and B). IL-17A overexpression selectively and significantly upregulated the expression of pro-angiogenic CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL8) in Huh7.5 cells and CXCL2 in HepG2 cells, whereas the expression of the angiostatic chemokine CXCL10 remained unaffected (Figure 1A and B). The expression levels of other CXC chemokines (data not shown) were extremely low or undetectable by RT-qPCR. These results were consistent with those obtained from experiments involving stimulation with recombinant IL-17A (Figure 1C and D). The researchers further confirmed these findings by using ELISA to measure the secretion of VEGFA, CXCL2, and CXCL10 in the presence or absence of recombinant IL-17A, as well as in IL-17A or EGFP-overexpressing cells (Figure 1E and F). These data suggest that pro-angiogenic CXC chemokines upregulated by IL-17A may promote angiogenesis in hepatocellular carcinoma.

Figure 1. IL-17A upregulates the production of pro-angiogenic CXC chemokines in liver cancer cells. (Liu L, et al., 2019)