Essential role of MMP-2 in carbon nanotube-induced invasion of human pleural mesothelial cells.

Details

• Personal Author:
  Dinu C-Z ; Liu Y ; Lohcharoenkal W ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Carcinogens Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Exposure-limits; Lung; Lung-cancer; Cancer; Nanotechnology; Humans; Cell-function; Cellular-function; Lung-tissue; Carcinogens; Carcinogenesis; Genes
• ISSN:
  0008-5472
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  73
• Issue:
  8
• NIOSHTIC Number:
  nn:20043956
• Citation:
  Cancer Res 2013 Apr; 73(8)(Suppl 1):4921
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Cancer Research. Proceedings of the AACR 104th Annual Meeting, April 6-10, 2013, Washington, DC
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/248236/cdc_248236_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]