主题:【分享】武汉大学科学家解析结肠癌抑制因子

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4月11日,《公共科学图书馆—综合》(PLOS ONE)杂志发表了武汉大学基础医学院和美国M.D.安德森癌症中心的科学家的研究论文,解析了IL-17细胞因子家族成员IL-17F对于结肠癌发生发展的影响及其分子机制。

Th17是一种近年来被发现的在炎症性疾病和自身免疫疾病中起主导作用的效应T细胞,其产生的特征性细胞因子白介素17 (IL-17)越来越广泛地受到关注。迄今为止,已发现了六个IL-17家族成员IL-17 A、IL-17B、IL-17C、IL-17D、IL-17E(亦命名为IL-25)和IL-17F,以及五个IL-17受体(IL-17RA-IL-17RE)家族成员。其中IL-17F与IL-17A具有最高同源性。有研究证实IL-17F在免疫反应中发挥多重功能。过去的研究表明IL-17A在癌症形成中发挥重要作用,然而对于IL-17F是否也在肿瘤形成中起作用却并不清楚。

研究人员证实IL-17F表达于正常人类结肠上皮细胞中,然而在结肠癌组织中IL-17F的表达显著减低。为了进一步检测IL-17F在结肠癌中的作用。研究人员对IL-17F过表达的结肠癌细胞系和IL-17F缺陷小鼠进行了研究。研究人员在小鼠实验中证实相比于移植到小鼠体内的对照组细胞,转染IL-17F的结肠癌细胞生长显著减慢。IL-17F基因敲除小鼠在接受结肠癌细胞移植后肿瘤数目和肿瘤体积相较于野生型对照组大大增高。

这些结果表明IL-17F在结肠癌形成中发挥了重要的抑制作用。在IL-17F过表达的肿瘤中,研究人员未发现白细胞渗出发生显著改变,然而却证实VEGF水平和CD31+细胞出现下降。在IL-17F缺陷结肠癌小鼠组织中VEGF水平则显著增高。

新研究结果表明IL-17F在结肠癌形成中发挥了保护性功能,而这一作用或有可能是通过抑制肿瘤血管形成而实现的。(
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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.
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