中性粒细胞是最快反应损伤和感染的一群细胞，但他们在癌症方面的作用却知之甚少。人们经常把肿瘤比喻为“永不愈合的伤口”。在临床肿瘤病人的病灶中经常发现丰富的中性粒细胞浸润。这些嗜中性粒细胞通过化学吸引，粘附和跨内皮迁移等类似于肿瘤细胞外渗转移过程一样响应招募。在某些情况下，嗜中性粒细胞通过细胞毒性作用或肿瘤特异性T细胞的募集抑制肿瘤，而在其他某些情况下，中性粒细胞又可以维持炎症促进肿瘤的进展。
近期nature 刊发了由Wculek和Malanchi等人的研究成果。他们的研究表明嗜中性粒细胞在小鼠模型中可以作为乳腺癌细胞转移性定植的主要驱动力。研究发现，一方面，嗜中性粒细胞可以浸润肺部并分泌促炎因子（leukotrienes，白三烯）来改变肺部血管通透性、刺激其他细胞粘附；另一方面，表达leukotrienes receptor的肿瘤细胞被招募到肺部。这种恶性的转移定植在敲除中性粒细胞分化相关基因或白三烯的生物合成相关基因时都未出现。通过这些结果的启发，Wculek和Malanchi又通过使用阻断白三烯合成的药物zileutin进行研究测试，发现zileutin可以强烈并且单一的抑制肺转移，而原发肿瘤和中性粒细胞计数保持基本未受影响。
总体而言，这项研究阐明了嗜中性粒细胞如何通过释放炎性信号改变局部微环境促进转移灶形成。这些结果表明，白三烯受体的表达和中性粒细胞数量可能是有用的临床诊断生物标志物。此外，使用的消炎药来改变炎症微环境可能是抑制转移进程的有效疗法。
原文来源：Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 2015 Dec 17;528(7582):413-7.
Abstract ：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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外泌体资讯网 也虐狗？Nature：中性粒细胞和肿瘤细胞的那段情
