Essential role of MMP-2 in carbon nanotube-induced invasion of human pleural mesothelial cells.
Lohcharoenkal-W; Liu-Y; Stueckle-TA; Dinu-C-Z; Wang-L; Rojanasakul-Y
Cancer Res 2013 Apr; 73(8)(Suppl 1):4921
Carbon nanotubes (CNTs) have increasingly been used in a wide variety of applications. However, because of their needle-shape morphology, biopersistence and mode of exposure similar to those of asbestos which is a known carcinogen causing lung mesothelioma, there has been a great concern about their potential carcinogenicity. In this study, we investigated the effect of long-term exposure of CNT on proliferative and invasive properties of human pleural mesothelial cells. We found that chronic exposure of human mesothelial Met5A cells to low-dose non-cytotoxic concentration of single-walled CNT (0.02 µg/cm2 for 25 weeks) in culture induced malignant transformation of the cells as indicated by their increased cell invasion and migration. Analysis of gene expression by real-time PCR array showed a 50-fold increase in MMP-2 expression in CNT-transformed cells as compared to passage-matched control cells. Western blot analysis of the protein expression confirmed the upregulation of MMP-2 in the transformed cells. Downregulation of MMP-2 in the transformed cells by short-hairpin RNA stable transfection effectively inhibited the MMP-2 activity in these cells as well as their invasive and migratory activities. These results indicate MMP-2 as a key regulator of the aggressive phenotype of mesothelial cells after chronic CNT exposure. This study fortifies the carcinogenic potential of CNT and reveals a novel mechanism that may be important in CNT-induced mesothelioma.
Exposure-limits; Lung; Lung-cancer; Cancer; Nanotechnology; Humans; Cell-function; Cellular-function; Lung-tissue; Carcinogens; Carcinogenesis; Genes
Cancer Research. Proceedings of the AACR 104th Annual Meeting, April 6-10, 2013, Washington, DC