Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
Pulmonary Division, Department of Medicine A, Münster University Hospital, Münster, Germany.
Oncogene. 2014 Mar 6;33(10):1239-48. doi: 10.1038/onc.2013.75. Epub 2013 Apr 8.
Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease. The aim of this study was to investigate the role of myeloid cell nuclear factor-κB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 (rela(Δ-/-)) to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild-type mice. In CS-exposed rela(Δ-/-) mice, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt/β-catenin pathway. In conclusion, myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth and has a role in the activation of Wnt/β-catenin signaling in tumor cells.
吸烟是肺癌（LC）和慢性阻塞性肺疾病（COPD）的最重要危险因素。本研究旨在探讨髓样细胞核因子-κB 在肿瘤细胞生长信号调节中的作用。我们使缺乏髓样 RelA/p65（rela(Δ-/-)）的小鼠发生转移性 LC 模型。香烟烟雾（CS）暴露显著增加了野生型小鼠中 Lewis 肺癌细胞肿瘤的增殖。在 CS 暴露的 rela(Δ-/-)小鼠中，肿瘤生长受到了很大抑制。癌症组织的转录组和途径分析表明，髓样细胞对包括 Wnt/β-连环蛋白途径在内的各种生长信号途径具有重要影响。总之，髓样 RelA/p65 是将烟雾引起的炎症与 LC 生长联系起来的必要条件，并且在肿瘤细胞中 Wnt/β-连环蛋白信号的激活中起作用。
