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Nature:中性粒细胞——乳腺癌肺转移的重要“帮凶”

来源:生物谷 2015-12-15 14:15

2015年12月15日讯 /生物谷BIOON/ --尽管科学家们已经在癌细胞靶向药物开发方面取得显著进展,但治疗转移性肿瘤的治疗方法通常不是特别有效。许多研究表明癌细胞对它们所处的微环境存在依赖性,因此靶向肿瘤中的非癌细胞组成成分可能是新型治疗方法开发的重要基础。但是人们对于肿瘤生长和转移过程中宿主应答所发挥的作用仍了解较少,限制了新型治疗方法的开发。
 
在一项发表在国际学术期刊Nature上的最新研究中,来自英国弗朗西斯克里克研究所的研究人员发现中性粒细胞是乳腺癌小鼠模型肺转移灶微环境中的一种主要组成成分,同时也是促进转移灶形成的一个重要推动因素。
 
早期研究已经证明中性粒细胞在炎症性应答过程中发挥重要作用,但关于中性粒细胞是否会促进肿瘤形成一直存在争议。
 
研究人员利用多种不同策略阻断了中性粒细胞向癌细胞转移位点的招募过程,结果表明中性粒细胞能够促进癌细胞转移,特别是转移起始过程。特别重要的是,研究人员还发现中性粒细胞能够产生一种化学物质,促进具有高度成瘤潜能的癌细胞富集从而扩张癌细胞池,帮助癌细胞在远端组织定植形成转移灶。
 
通过基因或药物方法抑制中性粒细胞内负责合成该化学物质的酶(Alox5)能够消除中性粒细胞的促癌转移活性,随后抑制转移灶形成。
 
总得来说,这项研究表明靶向肿瘤微环境中的特定组成成分在抗癌转移方面具有重要应用前景,同时也具有较高的效率,抑制中性粒细胞中的Alox5或可限制癌细胞转移,Alox5也将成为抗癌新靶点。(生物谷Bioon.com)
 
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Neutrophils support lung colonization of metastasis-initiating breast cancer cells
 
Stefanie K. Wculek Ilaria Malanchi
 
Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment1 suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial2, 3, 4. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.
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