Acquisition of cancer stem cell-like properties in human small airway epithelial cells after a long-term exposure to carbon nanomaterials. Issue 7 (5th June 2019)

• Record Type: Journal Article
• Authors: Kiratipaiboon, Chayanin; Stueckle, Todd A.; Ghosh, Rajib; Rojanasakul, Liying W.; Chen, Yi Charlie; Dinu, Cerasela Zoica; Rojanasakul, Yon
• Is Part Of: Environmental science. Volume 6:Issue 7(2019)
• Page Start: 2152
• Page End: 2170
• Publication Date: 2019-06-05
• Subjects: Environmental sciences -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/c9en00183b
• Languages: English
• ISSNs: 2051-8153

Abstract

Abstract : Carbon nanomaterials and asbestos fibers induce genotoxicity and cancer stem cell-like transformation in human small airway epithelial cells. Abstract : 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 breaks, and p53 downregulation, indicating the 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 marker 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 disease development.