Nature:衰老个体中特定代谢物的积累可促进肿瘤进展 

2020-08-20 MedSci原创 MedSci原创

考虑到越来越多的证据表明,癌细胞外在因素是调控肿瘤进展的关键,研究人员提出假设,衰老可能会产生一个支持肿瘤进展和攻击性的系统环境。

从65岁开始,人类患癌症的风险和相关的死亡率大幅增加。然而,我们对年龄与癌症之间复杂关系的理解仍处于初级阶段。几十年来,这种联系在很大程度上被归因于老年人接触诱变剂的时间增加。然而,这种观点并没有考虑到饮食,运动和靶向代谢老化的小分子的既定作用。

考虑到越来越多的证据表明,癌细胞外在因素是调控肿瘤进展的关键,研究人员提出假设,衰老可能会产生一个支持肿瘤进展和攻击性的系统环境。

在最近的一篇Nature杂志发表的论文中,为了验证这一假设,研究人员从30名年轻(年龄≤30岁)和30名老年(年龄≥60岁)健康供体获取人血清(HS),并用该血清培养人癌A549和HCC1806细胞。

已有的研究显示,促炎症因子在肿瘤进展中具有关键作用,也有助于年龄相关疾病的发生。然而,衰老血清的蛋白质组学分析并没有显示出一个普遍的促炎症特征,来解释研究人员在癌细胞中观察到的攻击性特性。

考虑到代谢干预措施的有效性,如饮食,运动和热量限制可以减轻癌症的易感性和进展,研究人员又检查了供体血清的代谢成分。在靶向代谢组学检测到的179种循环代谢物中,只有10种代谢物的改变具有统计学意义(双面t检验,P<0.5)。考虑到下面四个代谢物在衰老过程中已知或建议的作用,谷胱甘肽、精氨酸、谷氨酰胺和α-酮戊二酸的水平明显下降是意料之中的。

值得注意的是,只有三种代谢物在老年供体的血清中持续增加:磷酸烯醇丙酮酸、喹啉酸和甲基丙二酸(MMA)。

为了测试这三种代谢物中是否有任何一种负责诱导癌症进展,研究人员用每种代谢物处理A549细胞。只有MMA可以诱导一个完整的促进癌症进展的EMT样表型,包括E-cadherin下降,同时纤维蛋白和vimentin蛋白增加。

因此,随着年龄的增长发生的代谢改变可以产生有利于肿瘤的进展和侵略性的系统环境。

研究人员还追溯到MMA能够诱导SOX4的表达,从而引起转录重编程,使癌细胞具有攻击性。

因此,MMA的积累代表了衰老和癌症进展之间的联系,这表明MMA是一个很有希望的晚期癌症的治疗目标。

 

原始出处:

Ana P. Gomes et al. Age-induced accumulation of methylmalonic acid promotes tumour progression, Nature (2020). 

 

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    2020-09-01 liye789132251
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    2020-08-27 14818eb4m67暂无昵称

    学习了

    0

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    2020-08-20 ms3000000449926787

    了解一下

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1884605, encodeId=fd401884605ed, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Sep 01 03:02:13 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1659997, encodeId=c32a165999e05, content=<a href='/topic/show?id=24e82545262' target=_blank style='color:#2F92EE;'>#代谢物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25452, encryptionId=24e82545262, topicName=代谢物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c1225086772, createdName=旅苦化文_216, createdTime=Sun Dec 13 17:02:13 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1737213, encodeId=8d451e3721301, content=<a href='/topic/show?id=611e8312358' target=_blank style='color:#2F92EE;'>#肿瘤进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83123, encryptionId=611e8312358, topicName=肿瘤进展)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c47234265932, createdName=ms8435843352634314, createdTime=Thu Oct 29 19:02:13 CST 2020, time=2020-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=813801, encodeId=98458138011a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Thu Aug 27 08:20:58 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811607, encodeId=43c281160e3f, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Aug 20 23:02:25 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811580, encodeId=5a58811580fb, content=Emt很好的指征, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 21:36:36 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811469, encodeId=2f11811469ce, content=很好的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Thu Aug 20 17:54:10 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811465, encodeId=e4a481146574, content=👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3cf85200902, createdName=1473bc66m67暂无昵称, createdTime=Thu Aug 20 17:38:11 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-08-20 神盾医疗局局长Jack

    Emt很好的指征

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1884605, encodeId=fd401884605ed, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Sep 01 03:02:13 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1659997, encodeId=c32a165999e05, content=<a href='/topic/show?id=24e82545262' target=_blank style='color:#2F92EE;'>#代谢物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25452, encryptionId=24e82545262, topicName=代谢物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c1225086772, createdName=旅苦化文_216, createdTime=Sun Dec 13 17:02:13 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1737213, encodeId=8d451e3721301, content=<a href='/topic/show?id=611e8312358' target=_blank style='color:#2F92EE;'>#肿瘤进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83123, encryptionId=611e8312358, topicName=肿瘤进展)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c47234265932, createdName=ms8435843352634314, createdTime=Thu Oct 29 19:02:13 CST 2020, time=2020-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=813801, encodeId=98458138011a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Thu Aug 27 08:20:58 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811607, encodeId=43c281160e3f, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Aug 20 23:02:25 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811580, encodeId=5a58811580fb, content=Emt很好的指征, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 21:36:36 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811469, encodeId=2f11811469ce, content=很好的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Thu Aug 20 17:54:10 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811465, encodeId=e4a481146574, content=👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3cf85200902, createdName=1473bc66m67暂无昵称, createdTime=Thu Aug 20 17:38:11 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-08-20 rayms

    很好的研究

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1884605, encodeId=fd401884605ed, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Sep 01 03:02:13 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1659997, encodeId=c32a165999e05, content=<a href='/topic/show?id=24e82545262' target=_blank style='color:#2F92EE;'>#代谢物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25452, encryptionId=24e82545262, topicName=代谢物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c1225086772, createdName=旅苦化文_216, createdTime=Sun Dec 13 17:02:13 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1737213, encodeId=8d451e3721301, content=<a href='/topic/show?id=611e8312358' target=_blank style='color:#2F92EE;'>#肿瘤进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83123, encryptionId=611e8312358, topicName=肿瘤进展)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c47234265932, createdName=ms8435843352634314, createdTime=Thu Oct 29 19:02:13 CST 2020, time=2020-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=813801, encodeId=98458138011a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Thu Aug 27 08:20:58 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811607, encodeId=43c281160e3f, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Aug 20 23:02:25 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811580, encodeId=5a58811580fb, content=Emt很好的指征, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 21:36:36 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811469, encodeId=2f11811469ce, content=很好的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Thu Aug 20 17:54:10 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811465, encodeId=e4a481146574, content=👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3cf85200902, createdName=1473bc66m67暂无昵称, createdTime=Thu Aug 20 17:38:11 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-08-20 1473bc66m67暂无昵称

    👍

    0

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