Activated macrophages are crucial during acute PM2.5 exposure-induced angiogenesis in lung cancer.

Abstract

The importance of ambient particulate matter (PM2.5) in lung cancer progression is well established; however, the precise mechanisms by which PM2.5 modulates lung cancer development have not yet been determined. The present study demonstrated increased mRNA and protein expression levels of vascular endothelial growth factor in PM2.5-induced macrophages. However, no significant changes to the expression levels of angiogenic cytokines (vascular endothelial growth factor A, matric metallopeptidase 9, basic fibroblast growth factor and platelet-derived growth factor) were observed in the Lewis lung carcinoma (LLC) cell line in response to acute PM2.5 exposure. PM2.5-induced activated macrophages were revealed to upregulate angiogenic cytokine expression following the acute exposure of LLC cells to PM2.5-induced macrophage supernatant. In vivo, the pro-angiogenic and macrophage accumulation functions of PM2.5 were supported by the establishment of a polyvinyl alcohol sponge implantation mouse model. Furthermore, PM2.5 was demonstrated to increase angiogenesis and macrophage recruitment in mice that were subcutaneously injected with LLCs. These results indicated that PM2.5 increases angiogenesis, and macrophages are crucial mediators of PM2.5-induced angiogenesis in lung cancer. These findings may provide novel insights for the development of lung cancer treatment strategies.