Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer
Open Access
- 3 November 2015
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 5 (1), 16053
- https://doi.org/10.1038/srep16053
Abstract
The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. However, it remains unclear how IL-17 might contribute to tumor angiogenesis. In our study, IL-17 enhanced the formation of vessel-like tubes in HUVECs both directly (when HUVECs were incubated with IL-17) and indirectly (when HUVECs were incubated in conditioned cell media (CCM) from IL-17-treated cancer cells). Our results from experiments using siRNA-mediated knockdowns of STAT3 and GIV suggest that the effects of IL-17 were mediated by activating STAT3/GIV signaling in NSCLC cells and subsequently up-regulating its downstream target VEGF. Consistent with these findings, immunostaining experiments on human NSCLC tissues indicated that IL-17 and GIV expression were significantly and positively associated with increased tumor vascularity. The clinical significance of IL-17 was authenticated by our finding that the combination of intratumoral IL-17 + cells and GIV expression served as a better prognosticator for survival than either marker alone. Therefore, our finding highlights a novel aspect of STAT3/GIV pathway in the IL-17 promotes tumor angiogenesis of NSCLC.This publication has 51 references indexed in Scilit:
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