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Oncogene：RET的上调诱导胰腺癌的神经束浸润

2017-01-24 MedSci MedSci原创

RET胰腺癌神经浸润
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沿着神经扩散的肿瘤是一种神经周围入侵的现象，其在包括胰腺导管腺癌（PDAC）的各种癌症中十分常见。神经浸润与肿瘤的不良结局相关，但其具体机制仍不清楚。近期，一项发表在Oncogene杂志上的研究使用转基因Pdx-1-Cre / KrasG12D / p53R172H（KPC）小鼠模型，研究者们研究了PDAC神经入侵的机制。为了检测影响癌细胞的神经浸润的组织特异性因素，研究者们在Cx3cr1、GDN

沿着神经扩散的肿瘤是一种神经周围入侵的现象，其在包括胰腺导管腺癌（PDAC）的各种癌症中十分常见。神经浸润与肿瘤的不良结局相关，但其具体机制仍不清楚。

近期，一项发表在Oncogene杂志上的研究使用转基因Pdx-1-Cre / KrasG12D / p53R172H（KPC）小鼠模型，研究者们研究了PDAC神经入侵的机制。

为了检测影响癌细胞的神经浸润的组织特异性因素，研究者们在Cx3cr1、GDNF和CCR2转基因小鼠的神经束微环境中使用一系列骨髓移植（BMT）实验。

研究发现，在不同年龄的KPC小鼠中的肿瘤免疫标记和人癌症标本的分析显示在PDAC肿瘤发生期间RET表达上调。 

BMT实验显示，表达RET配体GDNF的BM衍生的巨噬细胞在癌侵袭的神经周围是高度丰富的。

使用来自CCR2缺陷供体的CSF-1R拮抗剂GW2580或BMT抑制神经周期巨噬细胞募集可以减少神经周围的浸润。

神经束膜的巨噬细胞缺失GDNF表达，或使用shRNA或小分子抑制剂抑制RET可以减少KPC小鼠PDAC的神经元入侵。

总之，此项研究结果表明，RET在胰腺肿瘤发生过程中上调，其活化诱导癌症周围神经浸润。BM衍生的巨噬细胞向神经周围微环境的转移和分泌GDNF是胰腺癌神经扩散的必要条件。

原始出处：
Amit M, Na'ara S, Leider-Trejo L, et al. Upregulation of RET induces perineurial invasion of pancreatic adenocarcinoma. Oncogene. 2017 Jan 16. doi: 10.1038/onc.2016.483.

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    2017-02-25 ysjykql

    #RET#

    0

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    2017-02-05 wmu姿

    新知识学习了

    0

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    2017-09-03 cy0324

    #Gene#

    0

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    2017-01-26 zsyan

    #Oncogene#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1913829, encodeId=acfe191382913, content=<a href='/topic/show?id=4684153e41f' target=_blank style='color:#2F92EE;'>#RET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15374, encryptionId=4684153e41f, topicName=RET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96d4340, createdName=ysjykql, createdTime=Sat Feb 25 11:39:00 CST 2017, time=2017-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=174340, encodeId=28071e434052, content=新知识学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=071c2012037, createdName=wmu姿, createdTime=Sun Feb 05 10:03:34 CST 2017, time=2017-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048768, encodeId=5ed92048e6875, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sun Sep 03 20:39:00 CST 2017, time=2017-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558057, encodeId=4c47155805eb4, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, 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=Thu Jan 26 05:39:00 CST 2017, time=2017-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172547, encodeId=61501e254753, content=不错不错，多读受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Wed Jan 25 14:40:17 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172475, encodeId=42251e24758a, content=好饿莫子好东西学习了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=92191944782, createdName=thlabcde, createdTime=Wed Jan 25 08:19:42 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172446, encodeId=ced31e244612, content=学习了，很好的内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJiaCBO9f33YY0a9cL4rhSH23PNEOVia2szWTbUl6IgFnukCuC2ptOD5mAC0Ax8qGt2pjwudkREHlmA/132, createdBy=d39e1630897, createdName=1dd8aa01m06(暂无匿称), createdTime=Wed Jan 25 03:33:23 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172409, encodeId=d9a71e240919, content=签到～～学习了～～, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eeef1960262, createdName=杨柳青青, createdTime=Tue Jan 24 20:27:00 CST 2017, time=2017-01-24, status=1, ipAttribution=)]
    2017-01-25 1e10c84am36(暂无匿称)

    不错不错，多读受益

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1913829, encodeId=acfe191382913, content=<a href='/topic/show?id=4684153e41f' target=_blank style='color:#2F92EE;'>#RET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15374, encryptionId=4684153e41f, topicName=RET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96d4340, createdName=ysjykql, createdTime=Sat Feb 25 11:39:00 CST 2017, time=2017-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=174340, encodeId=28071e434052, content=新知识学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=071c2012037, createdName=wmu姿, createdTime=Sun Feb 05 10:03:34 CST 2017, time=2017-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048768, encodeId=5ed92048e6875, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sun Sep 03 20:39:00 CST 2017, time=2017-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558057, encodeId=4c47155805eb4, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, 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=Thu Jan 26 05:39:00 CST 2017, time=2017-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172547, encodeId=61501e254753, content=不错不错，多读受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Wed Jan 25 14:40:17 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172475, encodeId=42251e24758a, content=好饿莫子好东西学习了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=92191944782, createdName=thlabcde, createdTime=Wed Jan 25 08:19:42 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172446, encodeId=ced31e244612, content=学习了，很好的内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJiaCBO9f33YY0a9cL4rhSH23PNEOVia2szWTbUl6IgFnukCuC2ptOD5mAC0Ax8qGt2pjwudkREHlmA/132, createdBy=d39e1630897, createdName=1dd8aa01m06(暂无匿称), createdTime=Wed Jan 25 03:33:23 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172409, encodeId=d9a71e240919, content=签到～～学习了～～, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eeef1960262, createdName=杨柳青青, createdTime=Tue Jan 24 20:27:00 CST 2017, time=2017-01-24, status=1, ipAttribution=)]
    2017-01-25 thlabcde

    好饿莫子好东西学习了！

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1913829, encodeId=acfe191382913, content=<a href='/topic/show?id=4684153e41f' target=_blank style='color:#2F92EE;'>#RET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15374, encryptionId=4684153e41f, topicName=RET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96d4340, createdName=ysjykql, createdTime=Sat Feb 25 11:39:00 CST 2017, time=2017-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=174340, encodeId=28071e434052, content=新知识学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=071c2012037, createdName=wmu姿, createdTime=Sun Feb 05 10:03:34 CST 2017, time=2017-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048768, encodeId=5ed92048e6875, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sun Sep 03 20:39:00 CST 2017, time=2017-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558057, encodeId=4c47155805eb4, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, 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=Thu Jan 26 05:39:00 CST 2017, time=2017-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172547, encodeId=61501e254753, content=不错不错，多读受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Wed Jan 25 14:40:17 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172475, encodeId=42251e24758a, content=好饿莫子好东西学习了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=92191944782, createdName=thlabcde, createdTime=Wed Jan 25 08:19:42 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172446, encodeId=ced31e244612, content=学习了，很好的内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJiaCBO9f33YY0a9cL4rhSH23PNEOVia2szWTbUl6IgFnukCuC2ptOD5mAC0Ax8qGt2pjwudkREHlmA/132, createdBy=d39e1630897, createdName=1dd8aa01m06(暂无匿称), createdTime=Wed Jan 25 03:33:23 CST 2017, time=2017-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172409, encodeId=d9a71e240919, content=签到～～学习了～～, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eeef1960262, createdName=杨柳青青, createdTime=Tue Jan 24 20:27:00 CST 2017, time=2017-01-24, status=1, ipAttribution=)]
    2017-01-25 1dd8aa01m06(暂无匿称)

    学习了，很好的内容

    0

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    2017-01-24 杨柳青青

    签到～～学习了～～

    0