Interleukin-9 promotes tumorigenesis through augmenting angiogenesis in non-small cell lung cancer.

IL-9 is a proinflammatory cytokine that plays a critical role in autoimmunity and inflammatory diseases. However, its role in tumorigenesis has not been well studied. In this study, we found that IL-9 expression was significantly increased and associated with poor progression in human non-small cell lung cancer (NSCLC). Ectopic expression of IL-9 in NSCLC cells did not affect cell proliferation and apoptosis in vitro, but markedly promoted tumor growth in vivo. Immune-profile analysis showed no significant changes in the frequencies of infiltrated immune cells in the tumor site, neither in nude mice nor in immune-competent mice. However, we found that VEGF and microvessel density (MVD) were significantly increased in xenografts. IL-9 could promote cell growth and tube formation of HUVEC cells in vitro. In addition, correlation analysis implied a significant positive relationship between the density of IL-9 and VEGF, as well as MVD in human NSCLC tissues. Finally, we found that IL-9 stimulated tumor angiogenesis via STAT3 signaling. Together, our findings demonstrate a promoting role of IL-9 in lung cancer development, probably through promoting tumor angiogenesis. IL-9 thus may represent a new prognostic marker and therapeutic target for NSCLC.