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Acquisition of Cancer Stem Cell-like Properties in Human Small Airway Epithelial Cells after a Long-term Exposure to Carbon Nanomaterials
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May 24 2019
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Source: Environ Sci Nano. 6(7):2152-2170
[PDF-2.34 MB]
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Alternative Title:Environ Sci Nano
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Description:Cancer stem cells (CSCs) are a key driver of tumor formation and metastasis, but how they are affected by nanomaterials is largely unknown. The present study investigated the effects of different carbon-based nanomaterials (CNMs) on neoplastic and CSC-like transformation of human small airway epithelial cells and determined the underlying mechanisms. Using a physiologically relevant exposure model (long-term/low-dose) with system validation using a human carcinogen, asbestos, we demonstrated that single-walled carbon nanotubes, multi-walled carbon nanotubes, ultrafine carbon black, and crocidolite asbestos induced particle-specific anchorage-independent colony formation, DNA-strand break, and p53 downregulation, indicating genotoxicity and carcinogenic potential of CNMs. The chronic CNM-exposed cells exhibited CSC-like properties as indicated by 3D spheroid formation, anoikis resistance, and CSC markers expression. Mechanistic studies revealed specific self-renewal and epithelial-mesenchymal transition (EMT)-related transcription factors that are involved in the cellular transformation process. Pathway analysis of gene signaling networks supports the role of SOX2 and SNAI1 signaling in CNM-mediated transformation. These findings support the potential carcinogenicity of high aspect ratio CNMs and identified molecular targets and signaling pathways that may contribute to the disease development.
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Pubmed ID:31372228
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Pubmed Central ID:PMC6675031
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Funding:R01 EB018857/NIBIB NIH HHS/National Institute of Biomedical Imaging and Bioengineering/United States ; R01 ES022968/NIEHS NIH HHS/National Institute of Environmental Health Sciences/United States ; P20 GM103434/NIGMS NIH HHS/National Institute of General Medical Sciences/United States ; P30 GM103488/NIGMS NIH HHS/National Institute of General Medical Sciences/United States ; S10 OD016165/ODCDC CDC HHS/Office of the Director/United States
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Volume:6
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Issue:7
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