Particulate Matter 2.5 Induces FGFR1-mediated Integrin Switch to Promote Non-small Cell Lung Cancer Metastasis.

Abstract

Background/aim: Particulate matter 2.5 (PM2.5) is known to adversely affect human health. While its involvement in lung cancer pathogenesis is recognized, its specific impact on metastasis-related behaviors of lung cancer cells remains largely unexplored.

Materials and methods: In this study, we employed cell culture models, proteomic analysis, and bioinformatic analysis. Target proteins and signaling pathways were validated using western blotting and immunofluorescence assay. Wound healing, transwell migration and phalloidin-rhodamine assays were used to determine the migratory activity.

Results: Proteomic analysis identified 3,795 proteins in both control and PM2.5-treated groups. Among these, proteins associated with metastasis, particularly those related to "cell migration" (GO: 0016477), were highlighted, identifying six key proteins involved in cancer metastasis. Protein-protein interaction analysis pinpointed fibroblast growth factor receptor 1 (FGFR1) as a central target influenced by PM2.5, which promoted cell migration via the Rap1 signaling pathway through integrin signaling. The enhanced migratory behavior of PM2.5-treated cells aligned with proteomic findings, demonstrating that PM2.5 exposure increases the motility of lung cancer cells. Western blotting and immunofluorescence confirmed that PM2.5 exposure led to up-regulation of FGFR1, integrin αV, β1, and activated p-Akt. Notably, PM2.5-treated cells exhibited significantly increased motility and a higher number of filopodia per cell.

Conclusion: These results indicate that FGFR1 is a crucial target in PM2.5-induced metastasis in lung cancer cells, operating through an FGFR1/integrin/Akt signaling axis. This study advances our understanding of the role of PM2.5 in lung cancer metastasis and suggests potential therapeutic strategies to mitigate cancer progression.