Neutrophil elastase in the tumor microenvironment.
Neutrophil elastase in the tumor microenvironment.
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DOI：
10.1016/j.steroids.2017.11.006
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发表时间：
2018-05
期刊：
影响因子：
2.7
通讯作者：
Hammes SR
中科院分区：
文献类型：
--
作者：
Lerman I;Hammes SR
在癌症的发生过程中，骨髓中髓系细胞的产生加速，循环和浸润性中性粒细胞以及粒细胞衍生的髓系抑制细胞(MDSCs)的数量与肿瘤的进展和患者的生存相关。因此，癌症能够劫持正常的宿主保护免疫系统，并利用它进一步促进生长和转移。髓系细胞根据肿瘤微环境中的提示分泌中性粒细胞弹性蛋白酶和中性粒细胞细胞外陷阱(NETs)，从而导致多种癌症类型的活性增强。中性粒细胞弹性蛋白酶可能确实是肿瘤发生的驱动力，因为在许多临床前研究中，基因缺失和药物抑制显著降低了肿瘤负担和转移潜力。在这篇综述中，我们考察了中性粒细胞弹性蛋白酶在癌症中作为刺激因子的现有证据，重点讨论了它促进原发肿瘤生长和继发器官转移的确切机制。最后，我们对中性粒细胞弹性蛋白酶抑制剂进行了简要的概述，并讨论了它们在癌症治疗中的潜在应用。
Myeloid cell production within the bone marrow is accelerated in the setting of cancer, and the numbers of circulating and infiltrating neutrophils and granulocytic myeloid derived suppressor cells (MDSCs) correlate with tumor progression and patient survival. Cancer is therefore able to hijack the normally host-protective immune system and use it to further fuel growth and metastasis. Myeloid cells secrete neutrophil elastase and neutrophil extracellular traps (NETs) in response to cues within the tumor microenvironment, thereby leading to enhanced activity in a variety of cancer types. Neutrophil elastase may indeed be a driver of tumorigenesis, since genetic deletion and pharmacological inhibition markedly reduces tumor burden and metastatic potential in numerous preclinical studies. In this review, we examine the current evidence for neutrophil elastase as a stimulatory factor in cancer, focusing on precise mechanisms by which it facilitates primary tumor growth and secondary organ metastasis. We conclude with a brief overview of neutrophil elastase inhibitors and discuss their potential use in cancer therapy.
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