Diesel exposure favors lung cancer progression through induction of an inflammatory microenvironment.

Abstract

Air pollution, especially fine particulate matter, is a major health problem. Several epidemiological studies have demonstrated a significant association between exposure to fine particles and the development of lung and cardiovascular diseases. However, underlying mechanisms of the impact of fine particles on the pathogenesis of lung cancer remain unclear. The aim of this study was to determine whether exposure to fine particles may create a lung microenvironment prone to lung cancer progression. C57BL/6 mice were exposed to diesel exhaust particles (DEP) by intratracheal instillations. After 2 instillations of DEP (200µg/mL), lungs were collected and the immune microenvironment was analyzed by flow cytometry. To evaluate whether the inflammatory microenvironment conditioned by DEP had an impact on tumor progression, Lewis Lung Carcinoma (LLC) tumor cells were orthotopically injected. Cytokines were measured in the bronchoalveolar lavage fluid (BALF) after DEP exposure by cytokine array. Finally, the effect of BALF of naïve or DEP-exposed mice on cancer cells attraction was tested. We demonstrate that lung tumor progression is higher in DEP-instilled mice as compared to control mice. BAL cell counts and FACS analysis have revealed an increase in neutrophils. Moreover, BALF of DEP-instilled mice had a higher chemoattractant effect on tumor cells as compared to control. The expression of 36 cytokines was significantly increased in the BALF of DEP-instilled mice and ongoing analysis will help identifying the key pro-tumor molecules. Exposure to DEP appears to create a supportive lung microenvironment for tumor progression in which recruited neutrophils are probably involved.