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髓过氧化物酶:在癌症发病机制中的重要性日益增加及作为潜在药物靶点的潜力。

Myeloperoxidase: Growing importance in cancer pathogenesis and potential drug target.

机构信息

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

出版信息

Pharmacol Ther. 2022 Aug;236:108052. doi: 10.1016/j.pharmthera.2021.108052. Epub 2021 Dec 8.

Abstract

Myeloperoxidase is a heme-peroxidase which makes up approximately 5% of the total dry cell weight of neutrophils where it is predominantly found in the primary (azurophilic) granules. Other cell types, such as monocytes and certain macrophage subpopulations also contain myeloperoxidase, but to a much lesser extent. Initially, the function of myeloperoxidase had been mainly associated with its ability as a catalyzer of reactive oxidants that help to clear pathogens. However, over the past years non-canonical functions of myeloperoxidase have been described both in health and disease. Attention has been specially focused on inflammatory diseases, in which an exacerbate infiltration of leukocytes can favor a poorly-controlled production and release of myeloperoxidase and its oxidants. There is compelling evidence that myeloperoxidase derived oxidants contribute to tissue damage and the development and propagation of acute and chronic vascular inflammation. Recently, neutrophils have attracted much attention within the large diversity of innate immune cells that are part of the tumor microenvironment. In particular, neutrophil-derived myeloperoxidase may play an important role in cancer development and progression. This review article aims to provide a comprehensive overview of the roles of myeloperoxidase in the development and progression of cancer. We propose future research approaches and explore prospects of inhibiting myeloperoxidase as a strategy to fight against cancer.

摘要

髓过氧化物酶是一种血红素过氧化物酶,约占中性粒细胞总干重的 5%,主要存在于初级(嗜天青)颗粒中。其他细胞类型,如单核细胞和某些巨噬细胞亚群也含有髓过氧化物酶,但含量要少得多。最初,髓过氧化物酶的功能主要与其作为活性氧化剂的催化能力有关,这些氧化剂有助于清除病原体。然而,在过去的几年中,髓过氧化物酶的非经典功能在健康和疾病中都有描述。人们特别关注炎症性疾病,在这些疾病中,白细胞的过度浸润可能会导致髓过氧化物酶及其氧化剂的产生和释放失控。有确凿的证据表明,髓过氧化物酶衍生的氧化剂有助于组织损伤以及急性和慢性血管炎症的发展和传播。最近,中性粒细胞在肿瘤微环境中作为固有免疫细胞的多样性中引起了广泛关注。特别是,中性粒细胞衍生的髓过氧化物酶可能在癌症的发展和进展中发挥重要作用。本文综述了髓过氧化物酶在癌症发展和进展中的作用,提出了未来的研究方法,并探讨了抑制髓过氧化物酶作为抗癌策略的前景。

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