4月11日,《公共科學(xué)圖書館—綜合》（PLOS ONE）雜志發(fā)表了武漢大學(xué)基礎(chǔ)醫(yī)學(xué)院和美國M.D.安德森癌癥中心的科學(xué)家的研究論文，解析了IL-17細(xì)胞因子家族成員IL-17F對于結(jié)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(dǎo)作用的效應(yīng)T細(xì)胞,，其產(chǎn)生的特征性細(xì)胞因子白介素17 (IL-17)越來越廣泛地受到關(guān)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(yīng)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(dá)于正常人類結(jié)腸上皮細(xì)胞中，然而在結(jié)腸癌組織中IL-17F的表達(dá)顯著減低,。為了進(jìn)一步檢測IL-17F在結(jié)腸癌中的作用,。研究人員對IL-17F過表達(dá)的結(jié)腸癌細(xì)胞系和IL-17F缺陷小鼠進(jìn)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(nèi)的對照組細(xì)胞,，轉(zhuǎn)染IL-17F的結(jié)腸癌細(xì)胞生長顯著減慢,。IL-17F基因敲除小鼠在接受結(jié)腸癌細(xì)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(jié)果表明IL-17F在結(jié)腸癌形成中發(fā)揮了重要的抑制作用,。在IL-17F過表達(dá)的腫瘤中,，研究人員未發(fā)現(xiàn)白細(xì)胞滲出發(fā)生顯著改變，然而卻證實VEGF水平和CD31+細(xì)胞出現(xiàn)下降。在IL-17F缺陷結(jié)腸癌小鼠組織中VEGF水平則顯著增高,。
新研究結(jié)果表明IL-17F在結(jié)腸癌形成中發(fā)揮了保護(hù)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.
