Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity

Details

• Personal Author:
  Castranova, Vincent ; Chen YC ; Dinu CZ ; Issaragrisil S ; Luanpitpong S ; Rojanasakul Y ; Wang L
• Description:
  Tumor microenvironment has been recognized as a key determinant of tumor formation and metastasis, but how tumor microenvironment is affected by nanomaterials is essentially unknown. Here, we investigated whether carbon nanotubes (CNTs), a widely used nanomaterial with known carcinogenic potential, can affect cancer-associated fibroblasts (CAFs), which are a key component of tumor microenvironment that provides necessary support for tumor growth. We show for the first time that single-walled CNT and to a lesser extent multi-walled and its COOH-functionalized form induced CAF-like cells, which are non-tumorigenic in animals, but promote tumor growth of human lung carcinoma and CNT-transformed lung epithelial cells. The mechanism by which CNT-induced CAF-like cells promote tumor growth involved the acquisition of cancer stem cells (CSCs) in cancer population. Gene knockdown experiments showed that an expression of podoplanin on CAF-like cells is essential for their effects, indicating the functional role of CAF-like cells and podoplanin in CNT tumorigenic process. Our findings unveil a novel mechanism of CNT-induced carcinogenesis through the induction of CAF-like cells that support CSCs and drive tumor formation. Our results also suggest the potential utility of podoplanin as a mechanism-based biomarker for rapid screening of carcinogenicity of CNTs and related nanomaterials for their safer design. [Description provided by NIOSH]
• Subjects:
  Biomarkers Carcinogens Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Cancer Carbon Nanotubes Carcinogenesis Carcinomas Cell Alteration Cellular Effects Fibroblasts Genes Lung Cancer Lung Cells Medical Screening Metastasis Multi-walled Carbon Nanotubes MWCNT Nanomaterials Nanotechnology Nanotubes Proteins Single-walled Carbon Nanotubes Stem Cells SWCNT Tumorigenesis Tumors

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• ISSN:
  2045-2322
• 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:
  6
• NIOSHTIC Number:
  nn:20049079
• Citation:
  Sci Rep 2016 Dec; 6:39558
• Contact Point Address:
  Sudjit Luanpitpong, Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
• Email:
  suidjit@gmail.com
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Scientific Reports
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2c49d746caf88978b85f2f40005bf9bb277568211d10e11480f10499969971d002a7c6b8c9d558a147d7580ddcc7c99a7100f49b95e45c504a45cd4c3ad91f22
• Download URL:
  https://stacks.cdc.gov/view/cdc/203654/cdc_203654_DS1.pdf
• File Type:
  [PDF - 2.31 MB ]