Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro

• Published in: Toxicology in vitro 2021-06, Vol.73, p.105126-105126, Article 105126
• Main Authors: Sridharan, Sreepradha, Taylor-Just, Alexia, Bonner, James C.
• Format: Article
• Language: English
• Subjects: Animals; Asbestos; Biomarkers; Biomedical materials; Carbon nanotubes; Carcinogenicity; Carcinogens; Cell Line; Cell Transformation, Neoplastic - genetics; Chronic exposure; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Exposure; Gene expression; Genetic transformation; Inhalation; Invasiveness; Lung cancer; Male; Mesothelial cells; Mesothelioma; Mesothelioma - genetics; Multi wall carbon nanotubes; Nanomaterials; Nanotechnology; Nanotubes; Nanotubes, Carbon - toxicity; Osteopontin; Osteopontin - genetics; Phenotypes; Pleura; Pleura - cytology; Polymerase chain reaction; Rats; Rats, Inbred F344; Respiration; RNA, Messenger; Transformations
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2021.105126

Mesothelioma is a cancer of the lung pleura primarily associated with inhalation of asbestos fibers. Multi-walled carbon nanotubes (MWCNTs) are engineered nanomaterials that pose a potential risk for mesothelioma due to properties that are similar to asbestos. Inhaled MWCNTs migrate to the pleura in rodents and some types cause mesothelioma. Like asbestos, there is a diversity of MWCNT types. We investigated the neoplastic potential of tangled (tMWCNT) versus rigid (rMWCNT) after chronic exposure using serial passages of rat mesothelial cells in vitro. Normal rat mesothelial (NRM2) cells were exposed to tMWCNTs or rMWCNTs for 45 weeks over 85 passages to determine if exposure resulted in transformation to a neoplastic phenotype. Rat mesothelioma (ME1) cells were used as a positive control. Osteopontin (OPN) mRNA was assayed as a biomarker of transformation by real time quantitative polymerase chain reaction (qPCR) and transformation was determined by a cell invasion assay. Exposure to rMWCNTs, but not tMWCNTs, resulted in transformation of NRM2 cells into an invasive phenotype that was similar to ME1 cells. Moreover, exposure of NRM2 cells to rMWCNTs increased OPN mRNA that correlated with cellular transformation. These data suggest that OPN is a potential biomarker that should be further investigated to screen the carcinogenicity of MWCNTs in vitro. [Display omitted] •Carbon nanotubes (tangled or rigid) were tested for neoplastic transformation of normal pleural mesothelial cells in vitro.•Rigid carbon nanotubes caused loss of cell contact inhibition and increased cell migration in an invasion assay.•Osteopontin mRNA expression was increased in mesothelial cells over certain passages by rigid carbon nanotubes.•Osteopontin is a potential biomarker for screening the neoplastic potential of carbon nanotubes in vitro.