Thirdhand smoke exposure promotes gastric tumor development in mouse and human

作者：Chengfei Jiang, Lingyan Chen, Chunping Ye, Suzaynn F. Schick, Peyton Jacob, Yingjia Zhuang, Jamie L. Inman, Changbin Chen, Lara A. Gundel, Hang Chang, Antoine M. Snijders, Xiaoping Zou, Jian‐Hua Mao, Bo Hang, Pin Wang · 发表于：Environment International · 年份：2024 · DOI：10.1016/j.envint.2024.108986 · 被引用次数：10 · 研究领域：Air Quality and Health Impacts、Heme Oxygenase-1 and Carbon Monoxide、Ferroptosis and cancer prognosis

• Thirdhand smoke (THS) exposure significantly increased gastric tumor incidence in CC036 mice. • THS induced over-expression of ECM genes in primary CC036 gastric epithelial cells. • CC036 derived THS gene signature has clinical value in human gastric cancer. • THS induces EMT providing a potential mechanism for THS-induced gastric cancer. • THS increased oncogenic traits in THS-treated human gastric cancer cell lines. The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo . In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 ( SPP1) and tribbles pseudokinase 3 ( TRIB3) emerging as potential targets through which THS may pro...