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 PM2.5 exposure initiates and aggravates lung carcinoma remain elusive. In the present study, we collected PM2.5 in Nanjing and explored the mechanisms underlying the oncogenic roles of PM2.5 in the murine lung carcinoma cell line LLC in vitro and in vivo. PM2.5 was closely attached to and internalized by lung cancer cells. Moreover, PM2.5 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 PM2.5 in vivo; our results suggested that the ARNT2/PP2A/STAT3/MMP-2 cascade played a key role in PM2.5-related oncogenicity. Finally, we observed that PM2.5 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 PM2.5, promoted the invasion of lung cancer cells via an ARNT2/PP2A/STAT3/MMP2 pathway, which may be targeted to alleviate the tumorigenic effect of PM2.5 in lung cancer.