A Protective Role by Interleukin-17F in Colon Tumorigenesis

作者:Tong, Zan*; Yang, Xuexian O.; Yan, Huichao; Liu, Weihuang; Niu, Xiaoyin; Shi, Yun; Fang, Wenfeng; Xiong, Bing; Wan, Yu; Dong, Chen
来源:PLos One, 2012, 7(4): e34959.
DOI:10.1371/journal.pone.0034959

摘要

Interleukin-17F (IL-17F), produced by Th17 cells and other immune cells, is a member of IL-17 cytokine family with highest homology to IL-17A. IL-17F has been shown to have multiple functions in inflammatory responses. While IL-17A plays important roles in cancer development, the function of IL-17F in tumorigenesis has not yet been elucidated. In the current study, we found that IL-17F is expressed in normal human colonic epithelial cells, but this expression is greatly decreased in colon cancer tissues. To examine the roles of IL-17F in colon cancer, we have used IL-17F over-expressing colon cancer cell lines and IL-17F-deficient mice. Our data showed decreased tumor growth of IL-17F-transfected HCT116 cells comparing to mock transfectants when transplanted in nude mice. Conversely, there were increased colonic tumor numbers and tumor areas in II-17f(-)/(-) mice than those from wild-type controls after colon cancer induction. These results indicate that IL-17F plays an inhibitory role in colon tumorigenesis in vivo. In IL-17F over-expressing tumors, there was no significant change in leukocyte infiltration; instead, we found decreased VEGF levels and CD31(+) cells. While the VEGF levels were increased in the colon tissues of Il-17f(-)/(-) mice with colon cancer. Together, our findings demonstrate a protective role for IL-17F in colon cancer development, possibly via inhibiting tumor angiogenesis.