Stathopoulos Georgios T, Sherrill Taylor P, Han Wei, Sadikot Ruxana T, Yull Fiona E, Blackwell Timothy S, Fingleton Barbara
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6840, USA.
Mol Cancer Res. 2008 Mar;6(3):364-71. doi: 10.1158/1541-7786.MCR-07-0309.
Epidemiologic and experimental evidence suggests that a link exists between inflammation and cancer, although this relationship has only recently begun to be elucidated for lung cancer, the most frequently fatal human tumor. Nuclear factor-kappaB (NF-kappaB), a transcription factor that controls innate immune responses in the lungs, has been implicated as an important determinant of cancer cell proliferative and metastatic potential; however, its role in lung tumorigenesis is uncertain. Here, we specifically examine the role of NF-kappaB-induced airway inflammation in lung cancer metastasis using a model of intravenous injection of Lewis lung carcinoma cells into immunocompetent C57Bl/6 mice. Induction of lung inflammation by direct and specific NF-kappaB activation in airway epithelial cells potentiates lung adenocarcinoma metastasis. Moreover, we identify resident lung macrophages as crucial effectors of lung susceptibility to metastatic cancer growth. We conclude that NF-kappaB activity in host tissue is a significant factor in the development of lung metastasis.
流行病学和实验证据表明，炎症与癌症之间存在联系，尽管这种关系直到最近才开始在肺癌（最常见的致命性人类肿瘤）中得到阐明。核因子-κB（NF-κB）是一种控制肺部固有免疫反应的转录因子，被认为是癌细胞增殖和转移潜能的重要决定因素；然而，其在肺癌发生中的作用尚不确定。在此，我们使用将Lewis肺癌细胞静脉注射到具有免疫活性的C57Bl/6小鼠体内的模型，专门研究了NF-κB诱导的气道炎症在肺癌转移中的作用。通过气道上皮细胞中直接和特异性的NF-κB激活来诱导肺部炎症，可增强肺腺癌转移。此外，我们确定驻留肺巨噬细胞是肺部对转移性癌生长易感性的关键效应细胞。我们得出结论，宿主组织中的NF-κB活性是肺转移发生的一个重要因素。
