Conditioned medium from 1-nitropyrene induced THP-1 foam cells promotes pro-tumorigenesis in lung epithelial cells

Diesel exhaust (DE) is a major environmental pollutant containing fine particulate matter and polycyclic aromatic hydrocarbons (PAHs). Among its constituents, 1-nitropyrene (1NP) is a recognized surrogate marker of DE. Although 1NP is known to induce oxidative stress and DNA damage in multiple cell types, its role in alveolar macrophage dysfunction and lung carcinogenesis remains poorly defined. In this study we observed that 1NP drives foam cell formation in THP-1-derived macrophages through activation of the aryl hydrocarbon receptor (AhR). Exposure to 1NP induced AhR nuclear translocation and lipid accumulation, as demonstrated by AhR immunofluorescence and Oil Red O/Nile Red staining, SEM analysis, while pharmacological inhibition of AhR markedly attenuated these effects. 1NP-induced foam cells displayed elevated IL-6 and TNF-α mRNA expression which correlated with increased secreted levels in the conditioned media and enhanced migratory behavior, both of which were suppressed by AhR inhibition. Importantly, conditioned media from 1NP-driven foam cells enhanced A549 pro-tumorigenic phenotypes, promoting colony formation, spheroid growth, and migration. These pro-tumorigenic effects were abolished when AhR was inhibited during foam cell induction, revealing AhR-dependent paracrine mechanism. Our findings identify a previously unrecognized role for 1NP-induced foam cells in establishing a tumor-supportive lung microenvironment and position AhR as a central molecular link between environmental toxicant exposure, immune cell remodeling, and cancer progression.