4月11日,《公共科學圖書館—綜合》(PLOS ONE)雜志發(fā)表了武漢大學基礎醫(yī)學院和美國M.D.安德森癌癥中心的科學家的研究論文,,解析了IL-17細胞因子家族成員IL-17F對于結腸癌發(fā)生發(fā)展的影響及其分子機制。
Th17是一種近年來被發(fā)現(xiàn)的在炎癥性疾病和自身免疫疾病中起主導作用的效應T細胞,,其產生的特征性細胞因子白介素17 (IL-17)越來越廣泛地受到關注,。迄今為止,已發(fā)現(xiàn)了六個IL-17家族成員IL-17 A,、IL-17B,、IL-17C、IL-17D,、IL-17E(亦命名為IL-25)和IL-17F,,以及五個IL-17受體(IL-17RA-IL-17RE)家族成員。其中IL-17F與IL-17A具有最高同源性,。有研究證實IL-17F在免疫反應中發(fā)揮多重功能,。過去的研究表明IL-17A在癌癥形成中發(fā)揮重要作用,然而對于IL-17F是否也在腫瘤形成中起作用卻并不清楚,。
研究人員證實IL-17F表達于正常人類結腸上皮細胞中,,然而在結腸癌組織中IL-17F的表達顯著減低。為了進一步檢測IL-17F在結腸癌中的作用,。研究人員對IL-17F過表達的結腸癌細胞系和IL-17F缺陷小鼠進行了研究,。研究人員在小鼠實驗中證實相比于移植到小鼠體內的對照組細胞,轉染IL-17F的結腸癌細胞生長顯著減慢,。IL-17F基因敲除小鼠在接受結腸癌細胞移植后腫瘤數(shù)目和腫瘤體積相較于野生型對照組大大增高,。
這些結果表明IL-17F在結腸癌形成中發(fā)揮了重要的抑制作用。在IL-17F過表達的腫瘤中,,研究人員未發(fā)現(xiàn)白細胞滲出發(fā)生顯著改變,,然而卻證實VEGF水平和CD31+細胞出現(xiàn)下降。在IL-17F缺陷結腸癌小鼠組織中VEGF水平則顯著增高,。
新研究結果表明IL-17F在結腸癌形成中發(fā)揮了保護性功能,,而這一作用或有可能是通過抑制腫瘤血管形成而實現(xiàn)的。(生物谷Bioon.com)
doi:10.1371/journal.pone.0034959
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A Protective Role by Interleukin-17F in Colon Tumorigenesis
Zan Tong, Xuexian O. Yang, Huichao Yan, Weihuang Liu, Xiaoyin Niu, Yun Shi, Wenfeng Fang, Bing Xiong, Yu Wan, Chen Dong
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 Il-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.