Nature：让肿瘤氧气供应正常化或是抵抗癌症的关键

2016-08-20 佚名生物谷

一项新的研究中，来自比利时天主教鲁汶大学等机构的研究人员作出一项主要的结论：肿瘤细胞中的氧气缺乏改变它们的基因表达，因而导致癌症生长。这一发现是影响深远的，这是因为它证实维持肿瘤中合适的氧气供应抑制这些所谓的“表观遗传异常（epigenetic aberration）”。这一认识可能最终导致人们开发出新的靶向血管或这些表观遗传异常的抗癌药物。相关研究结果于2016年8月17日在线发表在Nature

一项新的研究中，来自比利时天主教鲁汶大学等机构的研究人员作出一项主要的结论：肿瘤细胞中的氧气缺乏改变它们的基因表达，因而导致癌症生长。这一发现是影响深远的，这是因为它证实维持肿瘤中合适的氧气供应抑制这些所谓的“表观遗传异常（epigenetic aberration）”。这一认识可能最终导致人们开发出新的靶向血管或这些表观遗传异常的抗癌药物。相关研究结果于2016年8月17日在线发表在Nature期刊上，论文标题为“Tumour hypoxia causes DNA hypermethylation by reducing TET activity”。论文通信作者为来自天主教鲁汶大学的Diether Lambrechts教授和Bernard Thienpont博士。

一般而言，癌症发生已得到很好的理解：由于偶然性或致癌因子，单个细胞的DNA发生突变，随后这种异常的细胞发生快速地增殖。这些基因突变破坏正常的细胞功能，但是有利于癌细胞生长和存活。但是除了这些基因变化外，肿瘤细胞也在表观遗传上存在差异：它们不得不处理基因如何表达而不是这些基因本身。

与很多癌症相关联

尽管表观遗传变化并不影响遗传密码，但是它们能够类似地强烈地干扰基因功能，从而有利于癌细胞生长。但是在此之前，这些表观遗传变化的起源在很大程度上仍然是个谜。来自Lambrechts实验室的研究人员研究了一种常见的表观遗传变化：超甲基化（hypermethylation），或者说甲基基团过度地添加到DNA上。超甲基化阻止肿瘤抑制基因表达，因而能够让细胞产生异常行为和导致肿瘤过度生长。

Lambrechts说，“我们的研究发现这些表观遗传变化是由肿瘤所在的环境，更具体地说，氧气短缺所导致的。氧气是正常条件下移除DNA上的甲基基团的酶所需要的。当氧气缺乏时，太多的甲基基团保留下来，从而导致超甲基化。再者，缺氧解释了肿瘤中高达一半的超甲基化。尽管我们的大多数研究以乳腺癌为研究对象，但是我们也证实这种机制对膀胱癌、头颈癌、肾癌、肺癌和子宫瘤产生类似的广泛影响。”

诊断和治疗应用

揭示出氧气缺乏与肿瘤生长之间存在的这种关联性是分析3000多种病人肿瘤样品的结果。在下一步中，研究人员证实了另一个假设：干扰肿瘤的氧气供应能否阻止癌症发展？他们高兴地看到这种假设得到证实：在小鼠体内，他们证实让肿瘤的血液供应正常化足以阻止这些表观遗传变化发生。

Thienpont说，“我们在这项研究中获得的新认识能够对癌症控制产生潜在的巨大影响。首先，我们可能能够利用这些表观遗传变化监控肿瘤的氧气供应，从而允许我们更好地预测肿瘤行为和作出更加明智的治疗决策。再者，它对现存的血管靶向疗法产生新的认识。它们不仅有助转运化疗药物到肿瘤中，而且也有助抑制新的表观遗传变化。这可能能够有助让癌症复发变得不那么侵袭性，因而经证实是有治疗益处的。”

下一步

Lambrechts实验室如今正在验证分析肿瘤DNA是否能够被用来预测肿瘤含氧量。研究人员也在开展聚焦于血管正常化疗法的新研究。Lambrechts作出结论，“我们想要知道抑制甚至逆转这些表观遗传变化中的一些是否可能的。这些研究思路和其他新的研究方法让我们在未来的癌症研究中信心满满。”

原始出处

Bernard Thienpont,Jessica Steinbacher,Hui Zhao, Flora D’Anna,Anna Kuchnio, Athanasios Ploumakis,Bart Ghesquière,Laurien Van Dyck,Bram Boeckx,Luc Schoonjans,Els Hermans,Frederic Amant, Vessela N. Kristensen,Kian Peng Koh, Massimiliano Mazzone,Mathew L. Coleman,Thomas Carell,Peter Carmeliet & Diether Lambrecht.Tumour hypoxia causes DNA hypermethylation by reducing TET activity.Nature.2016

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2016-09-20 仁心济世

#Nat#

25 0
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2016-09-01 1771ae4158m

这个有意思

63 0
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2016-08-30 李东泽

很好，不错，以后会多学习

66 0
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2016-08-26 李东泽

这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。

70 0
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2016-08-26 李东泽

这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。

69 0
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2016-08-26 李东泽

这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。

57 0
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2016-08-22 医路开来

学习啦谢谢

30 0
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2016-08-22 fenqiuse

期待后续更多更具体的治疗方式

22 0
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2016-08-21 lecoo

如何个性话的治疗是难点。

30 0
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2016-08-21 1e0d99ddm02(暂无匿称)

学习一下！！

22 0