The role of neutrophil myeloperoxidase in models of lung tumor development.
The role of neutrophil myeloperoxidase in models of lung tumor development.
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DOI：
10.3390/cancers6021111
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发表时间：
2014-05-09
期刊：
影响因子：
5.2
通讯作者：
Vikis HG
中科院分区：
文献类型：
--
作者：
Rymaszewski AL;Tate E;Yimbesalu JP;Gelman AE;Jarzembowski JA;Zhang H;Pritchard KA Jr;Vikis HG
慢性炎症在肺癌中起着关键的促肿瘤作用。我们之前对小鼠的研究表明，中性粒细胞是甲基胆蒽 (MCA) 引发、丁基羟基甲苯 (BHT) 促进的肺癌发生中肿瘤促进的关键介质。在本研究中，我们研究了中性粒细胞髓过氧化物酶（MPO）活性在这种炎症促进模型中的作用。给予 BHT 的小鼠肺部 MPO 蛋白和活性水平增加。在炎症阶段用 N-乙酰赖氨酰酪氨酰半胱氨酸酰胺 (KYC)（一种新型 MPO 三肽抑制剂）治疗小鼠可减轻肿瘤负荷。在单独的肿瘤模型中，对小鼠 Lewis 肺癌 (LLC) 肿瘤移植物进行 KYC 治疗对肿瘤生长没有影响，然而，MPO 遗传缺陷的小鼠却显着降低了 LLC 肿瘤的生长。我们的观察表明 MPO 催化活性在肿瘤发展的早期阶段至关重要。然而，在肿瘤进展的后期阶段，似乎需要独立于催化活性的 MPO 表达。我们的研究主张在肺癌预防中使用 MPO 抑制剂。
Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.
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影响因子：
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