Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mol Carcinog. 2012 Dec;51(12):993-1002. doi: 10.1002/mc.20870. Epub 2011 Oct 17.
Multiple studies have shown a link between chronic inflammation and lung tumorigenesis. Inbred mouse strains vary in their susceptibility to methylcholanthrene (MCA)-initiated butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated whether neutrophils play a role in strain dependent differences in susceptibility to lung tumor promotion. We observed a significant elevation in homeostatic levels of neutrophils in the lungs of tumor-susceptible BALB/cByJ (BALB) mice compared to tumor-resistant C57BL/6J (B6) mice. Additionally, BHT treatment further elevated neutrophil numbers as well as neutrophil chemoattractant keratinocyte-derived cytokine (KC)/chemokine (C-X-C motif) ligand 1 (Cxcl1) levels in BALB lung airways. Lung CD11c+ cells were a major source of KC expression and depletion of neutrophils in BALB mice resulted in a 71% decrease in tumor multiplicity. However, tumor multiplicity did not depend on the presence of T cells, despite the accumulation of T cells following BHT treatment. These data demonstrate that neutrophils are essential to promote tumor growth in the MCA/BHT two-step lung carcinogenesis model.
多项研究表明，慢性炎症与肺肿瘤发生之间存在关联。近交系小鼠对甲基胆蒽（MCA）引发的丁羟甲苯（BHT）促进肺致癌作用的易感性存在差异。在本研究中，我们研究了中性粒细胞是否在对肺肿瘤促进的敏感性的种系依赖性差异中发挥作用。我们观察到，与肿瘤抗性 C57BL/6J（B6）小鼠相比，肿瘤易感 BALB/cByJ（BALB）小鼠肺部的中性粒细胞稳态水平显著升高。此外，BHT 处理进一步增加了 BALB 肺气道中的中性粒细胞数量以及中性粒细胞趋化因子角质细胞衍生细胞因子（KC）/趋化因子（C-X-C 基序）配体 1（Cxcl1）水平。肺 CD11c+细胞是 KC 表达的主要来源，BALB 小鼠中性粒细胞耗竭导致肿瘤多发性降低 71%。然而，尽管 BHT 处理后 T 细胞积聚，但肿瘤多发性并不依赖于 T 细胞的存在。这些数据表明，中性粒细胞是促进 MCA/BHT 两步肺致癌作用模型中肿瘤生长所必需的。
