Signal Transductions of BEAS-2B Cells in Response to Carcinogenic PM_2.5 Exposure Based on a Microfluidic System

Abstract

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.

Concentrations of Aerosol Numbers and Airborne Bacteria, and Temperature and Relative Humidity, and Their Interrelationships in a Tie-Stall Dairy Barn

“…Aerosols are fine solid particles or liquid droplets that are suspended in the air or gas [4]. Aerosol particles can carry abiotic inorganic substances such as metals (Zn, As, V) and organic substances (polycyclic aromatic hydrocarbons, PAHs) that are carcinogenic and promote the progression of cancer [5]. At present, aerosol particles are also considered as an essential contributor to climate change, the most severe environmental challenge humanity has to face, which threatens the well-being of the next generation.…”

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks

“…Other PM 2.5 components such as PAHs and metals can be internalized by cells not only in the cytoplasm but also in the mitochondria and nuclei, and this uptake is related to the activation of cell signaling pathways to promote the associated cell proliferation [20,21].…”

“…It appears that PM exposure represents a strong factor that dictates cell fate, with the participation of ROS, PAHs and metals in cell death induction [27]. PM 2.5 also causes an evasion of apoptosis in BEAS-2B cells through the PI3K-AKT pathway [20]. Interestingly, UFPs exhibit low levels of apoptosis, suggesting that the particles may cause impairment of mitochondrial-nuclear crosstalk, causing mitochondrial membrane depolarization, altered mitochondrial respiratory chain enzyme activity, and a reduction in the mitochondrial DNA copy number, altering redox homeostasis and inducing cell survival [28].…”

“…Exposure to PM 10 and PM 2.5 activates the NF-κB promoter and increases the levels and phosphorylation of NF-κB and its DNA binding activity, causing an anti-apoptotic effect on A549, BEAS-2B, murine alveolar macrophage RAW 264.7, and human umbilical vein endothelial cells (HUVEC) [26,[29][30][31][32][33][34][35]. Experiments using organ-level lung microfluidic systems have reported the induction of the anti-apoptotic pathways in lung epithelial cells [20]. The anti-apoptotic effect induced by PM 10 and PM 2.5 has been deeply investigated, and several signaling pathways including those involving oxidative stress are described [26,[33][34][35][36][37].…”

“…PM 2.5 induces endothelial cell cytoskeleton rearrangement causing a disruption of vascular integrity [43]. PAHs and metal components in PM 2.5 promote the activation of pro-angiogenic factors [20,21]. Mice exposed to PM showed an increased number of tumor nodules and elevated expressions of VEGF.…”