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Dev Cell:氨基酸才是癌细胞的很大营养源,或影响肿瘤治疗策略

2016-04-03 MHJ 科学之家

癌细胞能够不受控制地分裂,通过消耗葡萄糖维持自己的疯狂增殖,然后产生大量新的肿瘤细胞。此前,科学家们一直以为,产生新细胞的细胞群(包括癌细胞)营养物质大多来自于葡萄糖。然而,美国麻省理工学院(MIT)的生物学家们近日发现,虽然癌细胞消耗的氨基酸要比消耗的葡萄糖少,但氨基酸才是癌细胞的最大营养源。 这项研究为进一步了解癌细胞的新陈代谢提供了一种新方法。研究人员希望通过研究癌细胞的新陈代谢,研制出一种

How cancer cells fuel their growth

癌细胞能够不受控制地分裂,通过消耗葡萄糖维持自己的疯狂增殖,然后产生大量新的肿瘤细胞。此前,科学家们一直以为,产生新细胞的细胞群(包括癌细胞)营养物质大多来自于葡萄糖。然而,美国麻省理工学院(MIT)的生物学家们近日发现,虽然癌细胞消耗的氨基酸要比消耗的葡萄糖少,但氨基酸才是癌细胞的最大营养源。 这项研究为进一步了解癌细胞的新陈代谢提供了一种新方法。研究人员希望通过研究癌细胞的新陈代谢,研制出一种能够阻断癌细胞生长和分裂的新药物,从而从根本上治疗癌症。


MIT的研究人员Matthew Vander Heiden表示,如果想要成功地了解癌细胞新陈代谢的机制,他们首先需要明白细胞是通过哪些途径进行生长和分裂的。


细胞消耗了什么?


19世纪20年代,德国的生物化学家奥托•瓦博格发现癌细胞的产能方式与正常细胞不同,并提出了一个疑问——“为什么肿瘤细胞大量消耗葡萄糖却不能高效产能?”,这一疑问被称为"瓦博格效应(Warburg effect)"。葡萄糖是人体细胞的一种能量来源,人体细胞通过一系列需氧的复杂化学反应被葡萄糖分解。然而瓦博格发现,肿瘤细胞能够将自身的新陈代谢转变成一个不需要氧的发酵过程,这种代谢方式效率较低,产生的能量也比较少。


此后,科学家们又提出一些理论和假设,认为癌细胞利用这种低效代谢策略为新细胞保留和生产基本的营养物质。然而,这些假设存在一个漏洞,因为大多数的葡萄糖在被细胞分解后都转化为了乳酸盐,而乳酸盐是一种对细胞无用的人体排泄物。另外,科学家们也几乎没有研究过新产生的癌细胞或任何其他快速分裂的哺乳动物细胞的确切成分。因为哺乳动物吃的食物多种多样,因此似乎无法弄清楚究竟这些食物都分别为细胞的哪一部分提供了营养和能量。


为了弄清楚包括癌细胞在内的人体细胞是从哪些地方获取生长所需的基本营养物质,研究人员在培养皿中培养了几种不同类型的癌细胞和正常细胞。他们为这些细胞提供了含有碳和氮的不同营养物质,并根据每种细胞吸收的不同营养物做了标记,然后跟踪分析这些营养物质最终会变成什么。同时,研究人员还在这些细胞分裂前后分别测定了它们的质量,以计算每种营养物质在新生细胞群中所占的比例。


实验发现,尽管细胞消耗葡萄糖和谷氨酰胺(一种蛋白质合成中的编码氨基酸,哺乳动物非必需氨基酸,在体内可以由葡萄糖转变而来)的速度很快,但这两种分子对新细胞质量的贡献很少,葡萄糖贡献了10-15%的碳,谷氨酰胺贡献了大约10%的碳。而谷氨酰胺以外的其它氨基酸对细胞质量的贡献最大,它们贡献了新细胞质量中20-40%的碳原子,同时这些氨基酸还构成了蛋白质。


研究表明,人体细胞用一种更简单、也更直接的方式获取自身生长和分裂所需的基本营养物质。这就像建一座房子,你并没有从用泥土制作砖开始,而是直接用了你周围现有的砖。


重新聚焦瓦博格效应:为什么增殖的人体细胞会消耗大量的葡萄糖?


和此前的研究结果相似,研究人员发现,大多数的葡萄糖在被细胞分解后都转化为了乳酸盐,并被排了出去。因此,研究人员认为,细胞消耗大量的葡萄糖并不是为了产生碳,从而为细胞生长提供营养物质,而是因为它能为人体提供大量的能量。


目前,研究人员正在重新研究瓦博格效应,希望弄清楚这种效应是如何帮助细胞进行复制和分裂的。他们认为,瓦博格效应如何帮助细胞将葡萄糖转化为能量并不重要,重要的是为什么细胞将葡萄糖转化为乳酸盐的过程能够帮助其通过氨基酸分裂出更多的新细胞。


原始出处:


Hosios AM, Hecht VC, Danai LV, Johnson MO, Rathmell JC, Steinhauser ML, Manalis SR, Vander Heiden MG. Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells. Dev Cell. 2016 Mar 7;36(5):540-9. doi: 10.1016/j.devcel.2016.02.012.

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    2016-06-29 fzwish20000
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1982230, encodeId=dc5c198223099, content=<a href='/topic/show?id=13b658e849' target=_blank style='color:#2F92EE;'>#Dev#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5878, encryptionId=13b658e849, topicName=Dev)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bcaa382, createdName=fzwish20000, createdTime=Wed Jun 29 06:10:00 CST 2016, time=2016-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869324, encodeId=33ae186932444, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Jul 11 16:10:00 CST 2016, time=2016-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1860822, encodeId=06fa186082247, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Thu Dec 29 22:10:00 CST 2016, time=2016-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959580, encodeId=48e41959580e3, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Apr 29 14:10:00 CST 2016, time=2016-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79386, encodeId=d98be93867d, content=氨基酸的利弊谁更大, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eb851714505, createdName=1deaf99cm29(暂无匿称), createdTime=Mon Apr 18 20:15:00 CST 2016, time=2016-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79385, encodeId=1860e938561, content=涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eb851714505, createdName=1deaf99cm29(暂无匿称), createdTime=Mon Apr 18 20:14:00 CST 2016, time=2016-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=76604, encodeId=3f3be6604cc, content=希望人类尽快克服癌症, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbd11668261, createdName=小猫cathy, createdTime=Sat Apr 09 15:11:00 CST 2016, time=2016-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=76129, encodeId=13b3e6129e5, content=嗯嗯,学习了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=166, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cache2.medsci.cn/upload/content/day_160326/201603262025001865.jpg, createdBy=c7881618185, createdName=qian0416, createdTime=Wed Apr 06 22:06:00 CST 2016, time=2016-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=75503, encodeId=1b50e5503d2, content=确实很有意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90ea1614944, createdName=huangwukui, createdTime=Tue Apr 05 10:09:00 CST 2016, time=2016-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=75500, encodeId=baade55002a, content=不错,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLRP2D8sTDxkrGNjMqwyLUGd9Wbt6L0Yw9goia4ibPGLEx48lF9kvw86FKicbdWemTqujrf6K5WPIic8g/132, createdBy=69a11636814, createdName=ssummer, createdTime=Tue Apr 05 10:05:00 CST 2016, time=2016-04-05, status=1, ipAttribution=)]
    2016-04-29 维他命
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    2016-04-18 1deaf99cm29(暂无匿称)

    氨基酸的利弊谁更大

    0

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    2016-04-18 1deaf99cm29(暂无匿称)

    涨知识

    0

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    2016-04-09 小猫cathy

    希望人类尽快克服癌症

    0

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    2016-04-06 qian0416

    嗯嗯,学习了~

    0

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    2016-04-05 huangwukui

    确实很有意义

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=1982230, encodeId=dc5c198223099, content=<a href='/topic/show?id=13b658e849' target=_blank style='color:#2F92EE;'>#Dev#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5878, encryptionId=13b658e849, topicName=Dev)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bcaa382, createdName=fzwish20000, createdTime=Wed Jun 29 06:10:00 CST 2016, time=2016-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869324, encodeId=33ae186932444, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Jul 11 16:10:00 CST 2016, time=2016-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1860822, encodeId=06fa186082247, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Thu Dec 29 22:10:00 CST 2016, time=2016-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959580, encodeId=48e41959580e3, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Apr 29 14:10:00 CST 2016, time=2016-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79386, encodeId=d98be93867d, content=氨基酸的利弊谁更大, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eb851714505, createdName=1deaf99cm29(暂无匿称), createdTime=Mon Apr 18 20:15:00 CST 2016, time=2016-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79385, encodeId=1860e938561, content=涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eb851714505, createdName=1deaf99cm29(暂无匿称), createdTime=Mon Apr 18 20:14:00 CST 2016, time=2016-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=76604, encodeId=3f3be6604cc, content=希望人类尽快克服癌症, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbd11668261, createdName=小猫cathy, createdTime=Sat Apr 09 15:11:00 CST 2016, time=2016-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=76129, encodeId=13b3e6129e5, content=嗯嗯,学习了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=166, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cache2.medsci.cn/upload/content/day_160326/201603262025001865.jpg, createdBy=c7881618185, createdName=qian0416, createdTime=Wed Apr 06 22:06:00 CST 2016, time=2016-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=75503, encodeId=1b50e5503d2, content=确实很有意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90ea1614944, createdName=huangwukui, createdTime=Tue Apr 05 10:09:00 CST 2016, time=2016-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=75500, encodeId=baade55002a, content=不错,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLRP2D8sTDxkrGNjMqwyLUGd9Wbt6L0Yw9goia4ibPGLEx48lF9kvw86FKicbdWemTqujrf6K5WPIic8g/132, createdBy=69a11636814, createdName=ssummer, createdTime=Tue Apr 05 10:05:00 CST 2016, time=2016-04-05, status=1, ipAttribution=)]
    2016-04-05 ssummer

    不错,学习了

    0

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