Oncogene:阻断IL-3R-α能够通过靶向β-catenin途径来抑制肿瘤内皮细胞衍生的胞外囊泡(EV)介导的血管形成

2017-12-17 hzangs “外泌体之家”微信号

促血管生成细胞因子白细胞介素-3(IL-3)由乳腺癌和卵巢癌组织微环境中的炎性细胞释放,并且还充当人乳腺癌和肾肿瘤衍生的内皮细胞(TEC)的自分泌因子。我们以前已经表明,通过转移活性分子,IL-3处理的内皮细胞(EC)释放细胞外囊泡(EV),其可作为邻近EC的旁分泌机制。

摘要:促血管生成细胞因子白细胞介素-3(IL-3)由乳腺癌卵巢癌组织微环境中的炎性细胞释放,并且还充当人乳腺癌和肾肿瘤衍生的内皮细胞(TEC)的自分泌因子。我们以前已经表明,通过转移活性分子,IL-3处理的内皮细胞(EC)释放细胞外囊泡(EV),其可作为邻近EC的旁分泌机制。因此,本研究研究了抗IL-3R-α阻断抗体对从TECs释放的EV(抗-IL-3R-EV)促进血管生成作用的影响。我们发现抗IL-3R-EV治疗阻止了新生血管的形成,更重要的是,也诱导了体内TEC衍生的新生血管的消退。当比较天然TEC衍生的EV(EV)和抗IL-3R-EV的miR-内容物时,我们发现在不同水平靶向(Wnt)/β-catenin途径的两个miR被差异化调节。直接靶向β-catenin的miR-214-3p被上调,而靶向APC和GSK3β的miR-24-3p被下调。事实上,当它们转移到细胞中时,检测到“β-catenin破坏复合物”的两个成员的低β-联蛋白含量和高水平。此外,在用抗IL-3R-EVs,pre-miR-214-3p-EVs和antago-miR-24-3p-EV处理的TEC中发现c-myc下调,这与miR-214的网络分析-3p和miR-24-3p基因靶向一致。最后,体内研究已经证明pre-miR-214-3p-EV-和antago-miR-24-3p-EV处理的动物中血管的生长受损。当应用组合治疗时,这些效果变得更加明显。本研究的结果确定了经典的Wnt /β-catenin途径作为TEC衍生的EV促血管生成作用的相关机制。此外,我们在此提供的证据表明IL-3R阻断可能比miR靶向在通过改变TEC-EV-miR货物抑制幼稚TEC衍生的EV的促进血管形成效应方面产生一些显着的优势。

PS:文章关注了肿瘤血管生成过程,之前的研究已经表明IL-3在肿瘤血管生成中的作用,而本文介绍了只用IL-3R阻断剂来抑制该通路后阻断血管生成的表型及机制。机制落脚在miRNA,相对比较清晰明了。

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    2018-04-21 cy0324
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    2017-12-19 zsyan
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  6. [GetPortalCommentsPageByObjectIdResponse(id=2076669, encodeId=d1a520e666900, content=<a href='/topic/show?id=4c00549381e' target=_blank style='color:#2F92EE;'>#抑制肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54938, encryptionId=4c00549381e, topicName=抑制肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4736501, createdName=xiaoyang_ambs, createdTime=Tue Sep 04 02:00:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048947, encodeId=07f9204894e7a, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Apr 21 05:00:00 CST 2018, time=2018-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710112, encodeId=9a551e10112bd, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Thu Apr 05 06:00:00 CST 2018, time=2018-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558098, encodeId=95801558098aa, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Tue Dec 19 05:00:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599827, encodeId=d4fd159982eea, content=<a href='/topic/show?id=be324039e31' target=_blank style='color:#2F92EE;'>#囊泡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40397, encryptionId=be324039e31, topicName=囊泡)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=86bc18759177, createdName=charl1234573, createdTime=Tue Dec 19 05:00:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=270107, encodeId=86822e0107af, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Sun Dec 17 15:07:04 CST 2017, time=2017-12-17, status=1, ipAttribution=)]
    2017-12-17 戒馋,懒,贪

    谢谢分享学习了

    0