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

Details

• Alternative Title:
  Sci Rep
• Personal Author:
  Luanpitpong, Sudjit ; Wang, Liying ; Castranova, Vincent ; Dinu, Cerasela Zoica ; Issaragrisil, Surapol ; Chen, Yi Charlie ; Rojanasakul, Yon
• 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.
• Subjects:
  • AC133 Antigen
  • Animals
  • Biomarkers, Tumor
  • Cancer-Associated Fibroblasts
  • Cell Count
  • Cell Line, Tumor
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Epithelial Cells
  • Humans
  More +
• Source:
  Sci Rep. 2016; 6.
• Pubmed ID:
  27996035
• Pubmed Central ID:
  PMC5172236
• Document Type:
  Journal Article
• Volume:
  6
• Download URL:
  https://stacks.cdc.gov/view/cdc/43680/cdc_43680_DS1.pdf
• File Type:
  [PDF - 2.50 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:dc96308fd1e1e220f31dad27cc4e0c76449759e4e372eea5569b8cb6cc83777a