Fine Particulate Matter (PM2.5) Promoted the Invasion of Lung Cancer Cells via an ARNT2/PP2A/STAT3/MMP2 Pathway

Accumulating evidence indicates that fine particulate matter (PM2.5) exposure is associated with many cardiopulmonary diseases, particularly lung carcinoma. Nevertheless, the underlying biological mechanisms by which PM_2.5 exposure initiates and aggravates lung carcinoma remain elusive. In the present study, we collected PM_2.5 in Nanjing and explored the mechanisms underlying the oncogenic roles of PM_2.5 in the murine lung carcinoma cell line LLC in vitro and in vivo. PM_2.5 was closely attached to and internalized by lung Cancer cells. Moreover, PM_2.5 increased the production of ARNT2 and the inactivation of the tumor suppressor B56γ-PP2A, which was followed by the activation of ^ps727STAT3 and the enhancement of invasive ability by MMP-2. Furthermore, we took advantage of an orthotopic lung carcinoma metastasis mouse model to illustrate the prometastatic effect of PM_2.5 in vivo; our results suggested that the ARNT2/PP2A/STAT3/MMP-2 cascade played a key role in PM_2.5-related oncogenicity. Finally, we observed that PM_2.5 was deposited in human lung carcinoma tissues, indicating that this potential pathway may also be involved in human lung carcinoma. These findings demonstrated that fine particulate matter, or PM_2.5, promoted the invasion of lung Cancer cells via an ARNT2/PP2A/STAT3/MMP2 pathway, which may be targeted to alleviate the tumorigenic effect of PM_2.5 in lung Cancer.