Abstract 4921: Essential role of MMP-2 in carbon nanotube-induced invasion of human pleural mesothelial cells

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 4921
• Main Authors: Lohcharoenkal, Warangkana, Liu, Yuxin, Stueckle, Todd A., Dinu, Cerasela-Zoica, Wang, Liying, Rojanasakul, Yon
• Format: Journal Article
• Language: English
• Published: 15.04.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-4921

Abstract 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. Citation Format: Warangkana Lohcharoenkal, Yuxin Liu, Todd A. Stueckle, Cerasela-Zoica Dinu, Liying Wang, Yon Rojanasakul. Essential role of MMP-2 in carbon nanotube-induced invasion of human pleural mesothelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4921. doi:10.1158/1538-7445.AM2013-4921