Acquisition of Cancer Stem Cell-like Properties in Human Small Airway Epithelial Cells After a Long-term Exposure to Carbon Nanomaterials

Overview

Journal Environ Sci Nano

Publisher Royal Society of Chemistry

Date 2019 Aug 3

PMID 31372228

Citations 6

Authors

Chayanin Kiratipaiboon

Todd A Stueckle

Rajib Ghosh

Liying W Rojanasakul

Yi Charlie Chen

Cerasela Zoica Dinu

Yon Rojanasakul

Affiliations

Soon will be listed here.

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 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.

Citing Articles

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Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System.

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SOX2Mediates Carbon Nanotube-Induced Fibrogenesis and Fibroblast Stem Cell Acquisition.

Kiratipaiboon C, Voronkova M, Ghosh R, Rojanasakul L, Dinu C, Chen Y ACS Biomater Sci Eng. 2021; 6(9):5290-5304.

PMID: 33455278 PMC: 8215839. DOI: 10.1021/acsbiomaterials.0c00887.

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