Nature：脂肪是叛徒！为癌细胞扩散铺平道路

2016-12-30 佚名中国生物技术网

癌细胞一步步扩散到身体的其他部位，其方式是通过为自己“铺平道路”。于12月26日发表在《Nature》上的一项研究中，一个由和佛兰德斯生物技术研究所和比利时鲁汶大学(VIB-KU Leuven)的Peter Carmeliet博士领导的全球性跨学科研究团队发现，脂肪利用率增多是这些“道路”(即称为淋巴管的一种特殊血管)发育和生长的必要条件。这项研究为以靶向脂肪开发出限制淋巴管在癌症情况下增长铺平了

癌细胞一步步扩散到身体的其他部位，其方式是通过为自己“铺平道路”。于12月26日发表在《Nature》上的一项研究中，一个由和佛兰德斯生物技术研究所和比利时鲁汶大学(VIB-KU Leuven)的Peter Carmeliet博士领导的全球性跨学科研究团队发现，脂肪利用率增多是这些“道路”(即称为淋巴管的一种特殊血管)发育和生长的必要条件。这项研究为以靶向脂肪开发出限制淋巴管在癌症情况下增长铺平了道路。

癌细胞扩散是癌症最重要的以及对生命威胁最严重的并发症之一。目前的化疗和放疗虽然可以有效地治疗很多癌症，然而，癌细胞扩散到身体多个部位时将会导致癌症相关的死亡。癌细胞为了扩散的前提，必要找到一条已经存在的“道路”，或者开辟出一条新的“道路”。淋巴管比较特殊，它承担运输非血液的体液，它是癌细胞扩散的主要路径。淋巴管生成过程仍然不为人所了解，目前尚未有临床批准的药物能够阻止其在疾病期间增长。

脂肪为淋巴管提供能量

基于已经发表在一些顶级期刊上的研究，比如《Cell》和《Nature》，Brian Wong、Xingwu Wang、Annalisa Zecchin在Carmeliet教授的指导下，开始研究淋巴管的营养利用(代谢)。这项研究以一个简单的观察开始：相比于血管，淋巴管利用了更多的脂肪(脂肪酸)。这是对淋巴管利用营养物质的首次描述。使用药物抑制淋巴管的脂肪利用能够阻止淋巴管生长，这是将该发现转化为抑制癌症扩散手段的重要一步(Cell：抗癌革新发现，阻断糖酵解抑制血管新生)(Nature：让肿瘤氧气供应正常化或是抵抗癌症的关键)。

细胞所摄入的决定它们将成为什么

为了理解为什么这些细胞如此依赖脂肪，研究人员观察了淋巴系统是如何生成的。在胚胎发育过程中，淋巴会由血管转化而来。这项研究表明，将血管转化为淋巴管的信号也能够改变血管对“脂肪”的喜好。这项发现的新颖之处在于，这种转化依赖于脂肪利用的增长。在这个过程中，脂肪被用于生成一种分子，以修改重要的因子，这些因子调节基因序列的表达，即所谓的表观遗传变异，这可以确保淋巴管的功能。DNA并不会被脂肪改变，但是对定义淋巴基因标签的基因密码的利用会被调节。这项发现的一个重要方面是，另一种营养(脂肪)的再供应能够修复淋巴管的生长和功能。

Brian Wong博士说：“我们的研究表明，淋巴管对于脂肪的利用在它们的发育过程中被编程，对于淋巴的生长和功能是必要的。研究证明，通过加强或者阻止利用脂肪(或脂肪副产物)，我们能够控制淋巴管的生长。”

下一步工作

这项研究接下来的工作很清晰。一方面，对脂肪利用抑制剂进行大规模测试，验证它们在不同癌症中减轻癌症扩散的能力。另一方面，测试膳食脂肪补充(例如以运动员使用酮体的形式)是否能够治愈有缺陷的淋巴管，这是经历了癌症切除手术患者的常见并发症，通常会导致四肢肿胀，被称为淋巴水肿，目前无药可治。

Peter Carmeliet教授说：“我们接下来的工作是进一步将这些发现转化为癌症治疗所用。过去，我们没有开发出以淋巴管生长为靶标的药物，因为我们尚未理解它们如何发展起来的。这次的研究工作表明了淋巴管对脂肪依赖的重要性，并为开发出防止淋巴管过度生长和治疗淋巴管水肿并发症的药物提供了重要的步骤。”

原始出处：

Wong BW, Wang X, Zecchin A, Thienpont B, Cornelissen I, Kalucka J, García-Caballero M, Missiaen R, Huang H, Brüning U, Blacher S, Vinckier S, Goveia J, Knobloch M, Zhao H, Dierkes C, Shi C, Hägerling R, Moral-Dardé V, Wyns S, Lippens M, Jessberger S, Fendt SM, Luttun A, Noel A, Kiefer F, Ghesquière B, Moons L, Schoonjans L, Dewerchin M, Eelen G, Lambrechts D, Carmeliet P. The role of fatty acid β-oxidation in lymphangiogenesis. Nature. 2016 Dec 26. doi: 10.1038/nature21028

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2017-04-09 yb6572

#癌细胞扩散#

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2017-07-01 liye789132251

#Nat#

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2017-01-04 doctorJiangchao

继续学习

95 0
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2017-01-01 天涯183

最新研究成果

121 0
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2017-01-01 yxch36

#癌细胞#

86 0
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2016-12-31 Shirley_dai

有用

103 0
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2016-12-31 susice

饿死癌细胞

86 0

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