Nature重大发现：转移的乳腺癌细胞可自发改变“身份”

2016-08-25 佚名生物谷

在最近一项研究中美国麻省总医院的研究人员发现乳腺肿瘤细胞的分子特征可以发生自发性变化，使肿瘤变成一个混合细胞群体，并且由混合细胞群体组成的肿瘤需要同时使用几种不同的治疗药物进行治疗。相关研究结果发表在国际学术期刊Nature上。研究人员表示他们在最初诊断为ER阳性/HER2阴性的乳腺癌病人血液样本中发现HER2阳性和HER2阴性的循环肿瘤细胞同时存在，这些病人均发生了癌细胞转移。肿瘤的分子

在最近一项研究中美国麻省总医院的研究人员发现乳腺肿瘤细胞的分子特征可以发生自发性变化，使肿瘤变成一个混合细胞群体，并且由混合细胞群体组成的肿瘤需要同时使用几种不同的治疗药物进行治疗。相关研究结果发表在国际学术期刊Nature上。

研究人员表示他们在最初诊断为ER阳性/HER2阴性的乳腺癌病人血液样本中发现HER2阳性和HER2阴性的循环肿瘤细胞同时存在，这些病人均发生了癌细胞转移。

肿瘤的分子异质性是最近几年癌症治疗的一个干扰因素，需要使用多种药物特异性靶向不同的癌细胞群体。这项研究的目的在于进一步研究每个病人的肿瘤细胞中HER2表达的差异，以及这种差异性如何影响肿瘤生长和治疗。研究人员使用了一种叫做CTC-iChip的微流体装置来从血液样本中分离循环肿瘤细胞（CTC），结果发现18名病人中有16人的血液样本中同时存在HER2阳性和HER2阴性的CTC，这些病人在接受了ER阳性和HER2阴性乳腺癌靶向治疗后发生了癌细胞的转移。

研究人员将从这些病人体内分离得到的CTC进行培养也发现了HER2表达的类似特征，并且部分肿瘤细胞可以表达HER2，另外一些不表达。进一步检测这些HER2阳性肿瘤细胞发现一些参与生长信号途径的蛋白出现表达升高，但是HER2表达水平却没有像在HER2扩增原发性肿瘤中表达得那么高。

研究人员还发现这些HER2阳性细胞对HER2抑制剂药物的敏感性不比HER2阴性细胞更好，但将HER2抑制剂药物和IGFR1抑制剂药物组合使用能够对HER2阳性CTC产生毒性作用。

与之相比，HER2阴性CTC中参与Notch信号途径以及应答DNA损伤的一些信号途径的蛋白出现表达增加。除了这些差别，HER2阳性细胞增殖更快，能够对标准的化疗药物产生应答，而HER2阴性细胞对化疗药物抵抗性更强，但是对伽马分泌酶抑制剂更敏感。

研究人员还将HER2阳性和阴性的乳腺肿瘤细胞分别注射到小鼠的乳腺组织，诱导肿瘤发生。随后使用化疗药物紫杉醇治疗HER2阳性细胞占主导地位的肿瘤会导致肿瘤快速萎缩，但是之后会出现更多数量的HER2阴性细胞，而用紫杉醇治疗HER2阴性肿瘤则没有效果。将紫杉醇和一种伽马分泌酶抑制剂组合治疗混合了两种细胞的肿瘤，可以显著拖延肿瘤复发，这表明这种组合治疗策略有望清除混合肿瘤细胞群。

这两种肿瘤细胞群体来回转换表明一些可以同时靶向两个细胞群体的药物在治疗这类肿瘤方面可能会有非常重要的作用，不过这种转换机制还有待进一步研究。

原始出处

Nicole Vincent Jordan, Aditya Bardia, Ben S. Wittner, Cyril Benes, Matteo Ligorio, Yu Zheng, Min Yu.et.al.HER2 expression identifies dynamic functional states within circulating breast cancer cells.Nature.2016

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2017-04-30 仁心济世

#Nat#

63 0
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2017-05-29 ailian1202

#重大发现#

85 0
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2016-08-30 1771ae4158m

学习一下，好

81 0
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2016-08-30 李东泽

很好，不错，以后会多学习

101 0
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2016-08-29 靠近你

写的太好了，小编辛苦了，谢谢分享

102 0
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2016-08-27 yxch36

#癌细胞#

59 0
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2016-08-26 clivegranger

这篇资讯学习了

88 0
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2016-08-26 李东泽

这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。

81 0
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2016-08-26 1dd8a7c5m95(暂无匿称)

学习了，赞一个！！！

48 0
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encryptionId=41ef95e62c5, topicName=重大发现)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Mon May 29 13:55:00 CST 2017, time=2017-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=107733, encodeId=5fca10e73392, content=学习一下，好, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/11/23/ac01daf0962458a9eb8c0b1e2f6ce5bc.jpg, createdBy=04b81710322, createdName=1771ae4158m, createdTime=Tue Aug 30 22:13:00 CST 2016, time=2016-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=107536, encodeId=8b8510e5362a, content=很好，不错，以后会多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Tue Aug 30 15:00:00 CST 2016, time=2016-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=106776, encodeId=5461106e7610, content=写的太好了，小编辛苦了，谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=06731943211, createdName=靠近你, createdTime=Mon Aug 29 10:46:00 CST 2016, time=2016-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252126, encodeId=5cfb12521260d, content=<a href='/topic/show?id=3efee1519b2' target=_blank style='color:#2F92EE;'>#癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71519, encryptionId=3efee1519b2, topicName=癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cea26, createdName=yxch36, createdTime=Sat Aug 27 10:55:00 CST 2016, time=2016-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=104948, encodeId=a9df1049489d, content=这篇资讯学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=724c1678182, createdName=clivegranger, createdTime=Fri Aug 26 17:32:00 CST 2016, time=2016-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=104867, encodeId=1cab10486e35, content=这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 26 11:44:00 CST 2016, time=2016-08-26, status=1, ipAttribution=)]
2016-08-26 1dd8a7c5m95(暂无匿称)

学习了，赞一个！！！

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