Induction of stem-like cells with malignant properties by chronic exposure of human lung epithelial cells to single-walled carbon nanotubes

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• Personal Author:
  Castranova, Vincent ; Luanpitpong S ; Rojanasakul Y ; Wang L
• Description:
  Background: Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung cancer risks associated with chronic pulmonary exposure to single-walled (SW) CNT through the fundamental understanding of cellular and molecular processes leading to carcinogenesis. We hypothesized that the acquisition of cancer stem cells (CSC), a subpopulation that drive tumor initiation and progression, may contribute to CNT carcinogenesis. Methods: Non-tumorigenic human lung epithelial cells were chronically exposed to well-dispersed SWCNT for a period of 6 months at the physiologically relevant concentration of 0.02 mu g/cm(2) surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of CSC-like cells under CSC-selective conditions of tumor spheres and side population (SP). CSC-like cells were isolated using fluorescence-activated cell sorting and were assessed for aggressive behaviors, including acquired apoptosis resistance and increased cell migration and invasion in vitro, and tumor-initiating capability in vivo. Non-small cell lung cancer cells served as a positive control. Results: We demonstrated for the first time the existence of CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells. These CSC-like cells, in contrary to their non-CSC counterpart, possessed all biological features of lung CSC that are central to irreversible malignant transformation, self-renewal, aggressive cancer behaviors, and in vivo tumorigenesis. These cells also displayed aberrant stem cell markers, notably Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53 abrogated CSC properties of CSC-like cells. Furthermore, we identified specific stem cell surface markers CD24(low) and CD133(high) that are associated with SWCNT-induced CSC formation and tumorigenesis. Conclusions: Our findings provide new and compelling evidence for the acquisition of CSC-like cells induced by chronic SWCNT exposure, which are likely to be a major driving force for SWCNT tumorigenesis. Thus, our study supports prudent adoption of prevention strategies and implementation of exposure control for SWCNT. We also suggest that the detection of CSC and associated surface markers may provide an effective screening tool for prediction of the carcinogenic potential of SWCNT and related nanoparticles. [Description provided by NIOSH]
• Subjects:
  Biomarkers Carcinogens Environmental Monitoring Hazardous Substances Lung Lung Diseases Neoplasms Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Author Keywords: Carbon Nanotubes Cancer Carbon-compounds Carcinogenesis Cell-alteration Cell-damage Cell-migration Cell-transformation Cellular-reactions Chronic-exposure Disease-prevention Exposure-assessment Humans Lung-cancer Lung-cells Lung-disorders Lung Epithelial Cells Malignancy Malignant Transformation Medical-screening Nanotechnology Pulmonary-system-disorders Stem Cells Toxic-effects Toxic-materials Tumorigenesis Tumorigens

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• ISSN:
  1743-8977
• 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
• Pages in Document:
  22
• Volume:
  11
• NIOSHTIC Number:
  nn:20044628
• Citation:
  Part Fibre Toxicol 2014 May; 11:22
• Contact Point Address:
  Yon Rojanasakul, Pharmaceutical and Pharmacological Sciences Program, West Virginia University, Morgantown, WV 26506, USA
• Email:
  yrojan@hsc.wvu.edu
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Particle and Fibre Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a5ef20aa1943eb46a6582bf59aa90b2dc7edecdb9bf5123000c5f8768ed5f4ac02c15e605b820ab2c5e125d09aea4babc9253667f252473df51d4a2b9fcdf8fe
• Download URL:
  https://stacks.cdc.gov/view/cdc/200294/cdc_200294_DS1.pdf
• File Type:
  [PDF - 2.99 MB ]