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J Bone Oncol：研究揭示乳腺癌骨转移过程中内皮细胞改变的机制

2018-09-24 MedSci MedSci原创

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乳腺癌的进展和复发以及乳腺癌患者的存活率降低与慢性应激有关，慢性应激是一种已知会影响下丘脑-垂体轴和自主神经系统的疾病。临床前和临床证据支持交感神经系统参与控制骨重建和骨骼病理，包括骨转移。在骨转移的实验小鼠模型中，使用βAR激动剂异丙肾上腺素（ISO）作为交感神经元的主要神经递质去甲肾上腺素的替代物，可通过增加骨髓血管分布有利于转移性乳腺癌细胞的骨定植。然而，已知成功地将癌细胞外渗到远处器官中是

乳腺癌的进展和复发以及乳腺癌患者的存活率降低与慢性应激有关，慢性应激是一种已知会影响下丘脑-垂体轴和自主神经系统的疾病。临床前和临床证据支持交感神经系统参与控制骨重建和骨骼病理，包括骨转移。

在骨转移的实验小鼠模型中，使用βAR激动剂异丙肾上腺素（ISO）作为交感神经元的主要神经递质去甲肾上腺素的替代物，可通过增加骨髓血管分布有利于转移性乳腺癌细胞的骨定植。然而，已知成功地将癌细胞外渗到远处器官中是由活化的内皮介导的，其本身由炎症信号刺激。基于高交感神经流和炎性细胞因子的表达和骨转移之间的关联，因此，研究人员欲探究成骨细胞中的βAR刺激是否可以改变血管内皮以促进骨骼内的癌细胞植入。为了解决这个问题，我们使用来自PBS或ISO处理的骨髓基质细胞（BMSC）的条件培养基（CM）与骨髓内皮细胞（BMEC）或内皮细胞系C166进行粘附测定。

结果显示，ISO处理分化的BMSCs导致促炎细胞因子白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的强烈表达。来自ISO治疗的BMSCs的CM增加了BMECs中E-和P-选择素的表达以及人MDA-MB-231乳腺癌细胞在短期静态和动态粘附测定中与这些细胞的粘附，而阻断抗体IL-1β而非IL-6降低了这种作用。IL-1β直接处理BMECs产生类似的效果，而IL-6处理对BMECs的粘附分子表达和癌细胞与BMECs的粘附的影响可忽略不计。

总的来说，这些体外结果表明，在多细胞和动态骨髓环境的背景下，成骨细胞中的交感神经激活和随后的βAR刺激可以显著改变骨髓血管的密度，但也有利于骨髓血管的活化状态，有利于循环乳腺癌细胞的骨转移。

原始出处：

Lise Clément-Demange, Patrick L. Mulcrone, et al., β2ARs stimulation in osteoblasts promotes breast cancer cell adhesion to bone marrow endothelial cells in an IL-1β and selectin-dependent manner. J Bone Oncol. 2018 Nov; 13: 1–10.

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    2019-07-08 minlingfeng

    #Oncol#

    0

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    2019-05-12 apoenzyme

    #Bone#

    0

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    2018-09-25 lotus_nf

    学习中

    0

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    2018-09-24 xuexin53

    学习

    0

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    2018-09-24 1e1b8538m79(暂无匿称)

    不错的文章值得我有

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1865542, encodeId=b05b18655421f, content=<a href='/topic/show?id=16ce133504e' target=_blank style='color:#2F92EE;'>#Oncol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Mon Jul 08 10:35:00 CST 2019, time=2019-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1915188, encodeId=f20d19151882d, content=<a href='/topic/show?id=05343619cf' target=_blank style='color:#2F92EE;'>#Bone#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3619, encryptionId=05343619cf, topicName=Bone)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7dc7399, createdName=apoenzyme, createdTime=Sun May 12 00:35:00 CST 2019, time=2019-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=346502, encodeId=a9a034650257, content=学习中, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/09/24/0a9798be95f329f8aeea9747f116f25a.jpg, createdBy=5c461527451, createdName=lotus_nf, createdTime=Tue Sep 25 00:19:04 CST 2018, time=2018-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=346494, encodeId=45873464944c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4mzqK7XHyH86ToibWNdzamnZozW6yiceXFib4QHq1lCOia34v7bgwXUIH1Rdnoqia2y6ibLX156v1xmicZw/0, createdBy=15891613430, createdName=xuexin53, createdTime=Mon Sep 24 22:26:35 CST 2018, time=2018-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=346490, encodeId=edda3464909e, content=不错的文章值得我有, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Sep 24 22:19:27 CST 2018, time=2018-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=346473, encodeId=ee4c3464e3c7, content=学习了，长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Mon Sep 24 19:42:33 CST 2018, time=2018-09-24, status=1, ipAttribution=)]
    2018-09-24 1ddf0692m34(暂无匿称)

    学习了，长知识

    0

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