Role of mesothelin in carbon nanotube-induced carcinogenic transformation of human bronchial epithelial cells

Details

• Personal Author:
  Castranova, Vincent ; Chi A ; Despeaux E ; Dinu CZ ; He X ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated. MSLN overexpression was found in human lung tumors, lung cancer cell lines, and BSW cells. The functional role of MSLN in the BSW cells was then investigated by using stably transfected MSLN knockdown (BSW shMSLN) cells. MSLN knockdown resulted in significantly decreased invasion, migration, colonies on soft agar, and tumor sphere formation. In vivo, BSW shMSLN cells formed smaller primary tumors and less metastases. The mechanism by which MSLN contributes to these more aggressive behaviors was investigated by using ingenuity pathway analysis, which predicted that increased MSLN could induce cyclin E expression. We found that BSW shMSLN cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. Cell cycle analysis showed that the BSW shMSLN cells had an increased G2 population and a decreased S phase population, which is consistent with the decreased rate of proliferation. Together, our results indicate a novel role of MSLN in the malignant transformation of bronchial epithelial cells following CNT exposure, suggesting its utility as a potential biomarker and drug target for CNT-induced malignancies. [Description provided by NIOSH]
• Subjects:
  Asbestos Behavior Carcinogens Environmental Exposure Fibrosis Inorganic Chemicals Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Author Keywords: Mesothelin Cancer Carcinogenesis Cell Function Cell Invasion Cellular Function Exposure Levels Humans Lung Cells Mesothelial Cells Mesothelioma Morphology Nanotubes Pulmonary System Pulmonary System Disorders Respiratory System Disorders Risk Factors Toxic Effects Tumor Formation Tumorigenesis Tumors

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• ISSN:
  1040-0605
• Document Type:
  Text
• Genre:
  Journal Article
• 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:
  311
• Issue:
  3
• NIOSHTIC Number:
  nn:20048685
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2016 Sep; 311(3):L538-L549
• Contact Point Address:
  Y. Rojanasakul, Department of Pharmaceutical Sciences, West Virginia University, PO Box 9530, Morgantown, WV 26501
• Email:
  yrojan@hsc.wvu.edu
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9aae026b78c2f80150f4b1ed4cfe6bd84107cf0e88942fea3d9eb769c97ff3f6a437fa6d7acb3ee1fa2f17e1b5e7ffe3a0cf3457878669e51b4e4aec8adeb88a
• Download URL:
  https://stacks.cdc.gov/view/cdc/203381/cdc_203381_DS1.pdf
• File Type:
  [PDF - 4.88 MB ]