PDF(Pubmed)
Abstract：
Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo. Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke.
摘要：
肺癌是全球癌症相关死亡的主要原因。香烟烟雾在其发展和转移中起着关键作用。香烟烟雾也被认为是骨质流失疾病如骨质疏松症的危险因素。然而,香烟烟雾和另一种骨丢失障碍之间的联系，肺癌溶骨性骨转移，仍然很大程度上不确定。我们的基因集富集分析（GSEA）表明，肺癌患者中吸烟者表现出较高的骨转换基因集表达水平。癌症基因组图谱（TCGA）数据库和我们的临床样本均显示，在肺癌患者中有骨转移的吸烟者中，溶骨因子IL-6的表达升高。我们的细胞实验表明，苯并[α]芘（B[α]P）和香烟烟雾提取物（CSE）可促进肺癌中IL-6的产生和细胞迁移。激活PI3K，Akt,NF-κB信号通路参与香烟烟雾增强的IL-6依赖性迁移。此外,香烟烟雾肺癌分泌的IL-6促进破骨细胞形成。重要的是,阻断IL-6可在体内消除香烟烟雾促进的肺癌溶骨性骨转移。我们的发现提供了证据，表明香烟烟雾是溶骨性骨转移的危险因素。因此，抑制IL-6可能是控制吸烟肺癌患者溶骨性骨转移的一种有价值的治疗策略.
