title: Urotensin II contributes to the formation of lung adenocarcinoma inflammatory microenvironment through the NF-κB pathway in tumor-bearing nude mice.
abstract: Urotensin II (UII), a somatostatin-like cyclic peptide, was originally isolated from the fish urophysis. Our previous study showed that UII stimulates the proliferation of A549 lung adenocarcinoma cells and promotes tumor growth in a nude mouse xenograft model, suggesting that UII may contribute to the pathogenesis of lung adenocarcinoma. In this study, the underlying mechanism for UII to promote lung adenocarcinoma growth was explored by observing the effect of UII on the tumor inflammatory microenvironment in tumor-bearing nude mice. Immunohistochemical analysis showed that UII promoted the infiltration of CD68(+) tumor-associated macrophages (TAMs) in the tumor micro-environment. Enzyme-linked immunosorbent assay (ELISA) demonstrated that UII promoted the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9). Western blot analysis showed that UII promoted the activation of nuclear factor-κB (NF-κB). These findings suggest that the enhanced levels of IL-6, TNF-α and MMP-9 in the tumor microenvironment, which likely resulted from increased activation of NF-κB induced by UII, may be one of the important mechanisms by which UII promotes lung adenocarcinoma growth. These findings imply that antagonists of UII or urotensin II-receptor (UT-R) have potential for the prevention and treatment of lung adenocarcinoma.
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221004;
authors.forename: Cheng-Hua
authors.initials: CH
authors.lastname: Zhou
authors.forename: Ya-Ya
authors.initials: YY
authors.lastname: Wan
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Chu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Song
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Xing
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Wu
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Yin