Nat Commun:肿瘤适应低氧环境的分子机制被揭示,可能与小窝蛋白有关

2016-04-28 佚名 不详

2016年4月28日讯/生物谷BIOON/--靶向目标物在不伤害周围的健康组织的情况下可以进入癌细胞并传递致命细胞毒素。这在癌症研究中是一个长期的愿景,但它已经被证明很难实现。瑞典隆德大学的一个研究小组已经在这个方向上采取了一些重要措施。 Figure 1: Dynamics of constitutive membrane protein endocytosis. “多年来,我们试图

2016年4月28日讯/生物谷BIOON/--靶向目标物在不伤害周围的健康组织的情况下可以进入癌细胞并传递致命细胞毒素。这在癌症研究中是一个长期的愿景,但它已经被证明很难实现。瑞典隆德大学的一个研究小组已经在这个方向上采取了一些重要措施。

Figure 1: Dynamics of constitutive membrane protein endocytosis.
Dynamics of constitutive membrane protein endocytosis.

“多年来,我们试图阐明目标蛋白在癌细胞表面可以用来帮助这些“目标物质”进入细胞。发展这种方法非常复杂,但让我们感到很高兴的是终于成功了,”临床肿瘤学教授Mattias Beltin说。他的研究小组最近发表在Nature Communications上发表了新方法。

Mattias Belting描述了癌症肿瘤内部的不利环境。肿瘤的细胞快速分裂导致缺氧、低pH值、营养不足。在这样的环境下,一些癌细胞自发死亡,而其它癌细胞可以在辐射、化学或免疫疗法的作用下死亡。然而,一些癌细胞适应和生存能力非常强。

“我们称之为压力细胞,它们对常规的癌症治疗来说具有抵抗性。这些是我们必须寻找新的方法来杀死癌细胞的原因” Mattias Belting解释说。

隆德的研究人员绘制了数以千计存在于普通癌细胞表面的蛋白质,这些蛋白质在低氧环境下都 发生了改变。他们还发现了一种特殊的蛋白--小窝蛋白(caveolin-1)作为守护蛋白,防止许多表面蛋白进入压力癌细胞。在低氧环境下,它维护肿瘤细胞表面的蛋白质组的转换(蛋白质内化)起关键性作用,这一作用不依赖HIF。

研究者识别了大约30种目标蛋白质,存在于大量的压力癌细胞表面,它们有能力有效地通过守护蛋白,被运送到癌细胞中。对这些蛋白质之一,他们已经成功地设法靶向毒性结合目标蛋白,连接到一个特定的细胞毒素的某种抗体形式,它能够进入并杀死压力细胞,而其他细胞安然无恙。

“研究结果最重要的就是我们发现的蛋白质不仅存在于压力癌细胞中,其中一些也可以作为目标提供药物进入癌细胞中”该研究的第一作者Erika Bourseau-Guilmain说。

关于该研究项目研究组有相当大的兴趣。他们的方法和一些目标蛋白质在Nature Communications杂志上的文章中进行了详细的描述,使其他研究人员对该研究有了进一步了解。

“我们希望继续研究其他被识别的目标蛋白质。我们目前正在研究其他类型的压力细胞,用来开发潜在的目标蛋白质药物”Mattias Belting.说。

隆德研究人员曾研究过成胶质细胞瘤,它是脑瘤的一种,很难治疗。然而,他们相信“目标蛋白法”不仅可以用在这种类型,也可以用在其他许多类似的类型癌细胞中。

原始出处:

E. Bourseau-Guilmain, J. A. Menard, E. Lindqvist, V. Indira Chandran, H. C. Christianson, M. Cerezo Magaña, J. Lidfeldt, G. Marko-Varga, C. Welinder & M. Belting.Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells.doi:10.1038/ncomms11371 Nature Communications 7, Article number: 11371 doi:10.1038/ncomms11371

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1881011, encodeId=d4dd1881011e0, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Dec 04 11:13:00 CST 2016, time=2016-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=139341, encodeId=a6ae13934199, content=深度好文,值得关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, 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=Mon Oct 03 09:30:03 CST 2016, time=2016-10-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086859, encodeId=a853208685975, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Aug 06 00:13:00 CST 2016, time=2016-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=89114, encodeId=82338911482, content=目前缺氧与肿瘤研究很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=79401629895, createdName=Wuhuayan, createdTime=Thu Jun 09 08:37:00 CST 2016, time=2016-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=85183, encodeId=70148518345, content=学习了,很好的, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160509/IMG572FCF18A71237916.jpg, createdBy=d0861720708, createdName=stead, createdTime=Tue May 10 00:52:00 CST 2016, time=2016-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=85184, encodeId=d72e8518474, content=很不错的, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160509/IMG572FCF18A71237916.jpg, createdBy=d0861720708, createdName=stead, createdTime=Tue May 10 00:52:00 CST 2016, time=2016-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=83617, encodeId=134f8361e77, content=低氧一直研究的很火, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=86311671699, createdName=whwhah, createdTime=Tue May 03 19:50:00 CST 2016, time=2016-05-03, status=1, ipAttribution=)]
    2016-12-04 liye789132251
  2. [GetPortalCommentsPageByObjectIdResponse(id=1881011, encodeId=d4dd1881011e0, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Dec 04 11:13:00 CST 2016, time=2016-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=139341, encodeId=a6ae13934199, content=深度好文,值得关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, 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=Mon Oct 03 09:30:03 CST 2016, time=2016-10-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086859, encodeId=a853208685975, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Aug 06 00:13:00 CST 2016, time=2016-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=89114, encodeId=82338911482, content=目前缺氧与肿瘤研究很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=79401629895, createdName=Wuhuayan, createdTime=Thu Jun 09 08:37:00 CST 2016, time=2016-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=85183, encodeId=70148518345, content=学习了,很好的, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160509/IMG572FCF18A71237916.jpg, createdBy=d0861720708, createdName=stead, createdTime=Tue May 10 00:52:00 CST 2016, time=2016-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=85184, encodeId=d72e8518474, content=很不错的, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160509/IMG572FCF18A71237916.jpg, createdBy=d0861720708, createdName=stead, createdTime=Tue May 10 00:52:00 CST 2016, time=2016-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=83617, encodeId=134f8361e77, content=低氧一直研究的很火, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=86311671699, createdName=whwhah, createdTime=Tue May 03 19:50:00 CST 2016, time=2016-05-03, status=1, ipAttribution=)]
    2016-10-03 1e10c84am36(暂无匿称)

    深度好文,值得关注

    0

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    2016-08-06 liuli5079
  4. [GetPortalCommentsPageByObjectIdResponse(id=1881011, encodeId=d4dd1881011e0, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Dec 04 11:13:00 CST 2016, time=2016-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=139341, encodeId=a6ae13934199, content=深度好文,值得关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, 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=Mon Oct 03 09:30:03 CST 2016, time=2016-10-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086859, encodeId=a853208685975, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Aug 06 00:13:00 CST 2016, time=2016-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=89114, encodeId=82338911482, content=目前缺氧与肿瘤研究很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=79401629895, createdName=Wuhuayan, createdTime=Thu Jun 09 08:37:00 CST 2016, time=2016-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=85183, encodeId=70148518345, content=学习了,很好的, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160509/IMG572FCF18A71237916.jpg, createdBy=d0861720708, createdName=stead, createdTime=Tue May 10 00:52:00 CST 2016, time=2016-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=85184, encodeId=d72e8518474, content=很不错的, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160509/IMG572FCF18A71237916.jpg, createdBy=d0861720708, createdName=stead, createdTime=Tue May 10 00:52:00 CST 2016, time=2016-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=83617, encodeId=134f8361e77, content=低氧一直研究的很火, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=86311671699, createdName=whwhah, createdTime=Tue May 03 19:50:00 CST 2016, time=2016-05-03, status=1, ipAttribution=)]
    2016-06-09 Wuhuayan

    目前缺氧与肿瘤研究很多

    0

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    2016-05-10 stead

    学习了,很好的

    0

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    2016-05-10 stead

    很不错的

    0

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    2016-05-03 whwhah

    低氧一直研究的很火

    0

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