Cell Death Dis:RAGE在肺癌中发挥促癌作用

2020-05-09 QQY MedSci原创

RAGE(晚期糖基化终产物受体)是一种多配体受体,是免疫球蛋白超家族的成员。研究发现其与生理稳态、发育、炎症和多种疾病有关。此外,在各种类型的恶性肿瘤(包括前列腺癌、胃癌、乳腺癌和结肠癌)中,RAGE

RAGE(晚期糖基化终产物受体)是一种多配体受体,是免疫球蛋白超家族的成员。研究发现其与生理稳态、发育、炎症和多种疾病有关。此外,在各种类型的恶性肿瘤(包括前列腺癌、胃癌、乳腺癌和结肠癌)中,RAGE及其配体的表达水平均升高,被认为与癌症的转移和不良预后相关。

RAGE在正常肺组织中组成性表达,在肺癌组织中表达水平下调,而一些相反的研究结果发现RAGE介导的信号转导通路会促进肺癌发生。因此RAGE在肺癌发生发展过程中的作用还有待进一步的研究。

在该研究中,研究人员通过在人肺癌细胞系A549以及两个局部肺腺癌细胞系CL1-0和CL1-5中构建RAGE过表达稳转株,来验证RAGE对肺癌细胞的影响,并进一步通过移植瘤动物模型来评估RAGE在肺癌发生发展中的作用。

研究发现过表达RAGE会抑制A549细胞的生长。p53依赖性的p21CIP1的表达可以通过抑制CDK2激酶的活性和RB(成视网膜细胞瘤蛋白)的磷酸化来促进RAGE诱导的生长抑制作用。
 

另一方面,过表达RAGE可以通过ERK信号转导通路促进肺腺癌细胞的迁移、侵袭和间充质干细胞特性。此外,移植瘤实验发现RAGE能够通过上调p21CIP1的表达、激活ERK和EMT标记的变化促进肺癌细胞的转移。
 

进一步研究TAM(肿瘤相关的巨噬细胞)在肿瘤微环境中参与的作用,研究人员发现在移植瘤组织切片中TAM相关标记分子CD68和CD163以及血管生成相关标记分子CD31均有表达。研究数据显示,RAGE可能诱导肺癌细胞中TAM的累积来进一步促进体内肿瘤的生长。
 

总而言之,该研究揭示了RAGE在肿瘤的生长和转移中的作用及其相关机制,提示RAGE在肺癌中发挥致癌作用。

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    2021-03-03 维他命
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    2021-03-03 changhe722
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    2020-05-11 cy0328
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    2020-05-10 骚波哥哥

    谢谢分享

    0

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    2020-05-10 njwbhuang

    感谢分享!

    0

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