Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University , 220 Handan Road, Shanghai 200433, P.R. China.
Institute of Biomedical Science, Fudan University , Shanghai 200433, P.R.China.
Anal Chem. 2017 May 16;89(10):5413-5421. doi: 10.1021/acs.analchem.7b00218. Epub 2017 May 3.
PM (particulate matter less than 2.5 μm in diameter) is considered as a harmful carcinogen. Determining the precise relationship between the chemical constituents of PM in the air and cancer progression could aid the treatment of environment related disease and establishing risk reduction strategies. Herein, we used transcriptomics (RNA-seq) and an integrated microfluidic system to identify the global gene expression and differential target proteins expression induced by ambient fine particles collected from the heavy haze in China. The results clearly indicated that cancer related pathways exhibited the strongest dysregulation. The ambient fine particles could be uptaken into the cells by pinocytosis, mainly promoting the PI3K-Akt pathway, FGF/FGFR/MAPK/VEGF signaling, and the JAK-STAT pathway, leading to evading apoptosis, sustained angiogenesis, and cell proliferation, which are the most important hallmarks of cancer. And fine particles also have been demonstrated to create intracellular reactive oxygen species (ROS) and mitochondrial ROS, change intracellular free Ca, and induce apoptosis, which are all key players in mediating cancer progression. It was observed by transmission electron microscopy (TEM) that the particles from the haze could enter the mitochondria, resulting in disturbance of the mitochondrial membrane and disruption of the mitochondria, and these particles can even enter inside the nucleus. It was also found in our study of organics (OC, PAHs) and metals (Zn, As, V) that compounds of fine particles were more closely associated with the exacerbation of cancer and secondary aerosols generated by traffic had the largest impact on cancer related signal transductions.
PM（直径小于 2.5μm 的颗粒物）被认为是一种有害的致癌物质。确定空气中 PM 的化学成分与癌症进展之间的确切关系，可以帮助治疗与环境有关的疾病和制定降低风险的策略。在这里，我们使用转录组学（RNA-seq）和集成的微流控系统来鉴定来自中国重霾的环境细颗粒物引起的全局基因表达和差异靶蛋白表达。结果清楚地表明，癌症相关途径表现出最强的失调。环境细颗粒物可以通过胞饮作用被细胞摄取，主要促进 PI3K-Akt 途径、FGF/FGFR/MAPK/VEGF 信号转导和 JAK-STAT 途径，导致逃避细胞凋亡、持续血管生成和细胞增殖，这是癌症最重要的标志。而且，细颗粒物还被证明可以产生细胞内活性氧（ROS）和线粒体 ROS，改变细胞内游离 Ca，并诱导细胞凋亡，这些都是介导癌症进展的关键因素。透射电子显微镜（TEM）观察到，霾中的颗粒可以进入线粒体，导致线粒体膜紊乱和线粒体破坏，这些颗粒甚至可以进入细胞核。我们还发现，在对有机物（OC、PAHs）和金属（Zn、As、V）的研究中，细颗粒的化合物与癌症的恶化更密切相关，交通产生的二次气溶胶对癌症相关信号转导的影响最大。
