Whole genome expression signature of SWCNT sub-chronically exposed to human bronchial epithelial cells

ABSTRACT: Carcinogenicity of carbon nanotubes is a major concern but has not been well addressed due to the lack of experimental models. Here, we show that chronic exposure to single-walled carbon nanotubes causes malignant transformation of human lung epithelial cells. The transformed cells induce tumorigenesis in mice and exhibit an apoptosis resistant phenotype characteristic of cancer cells. In addition, cancer stem cells (CSCs), a subpopulation that drives tumor growth and progression, may represent targets for carcinogenic initiation by chemical and environmental agents. Transformed B-SWCNT also exhibited emergence of lung CSCs, as indicated by the induction of CSC tumor spheres and side population (SP). These CSCs, which were found to overexpress tumor promoter caveolin-1 (Cav-1), displayed aggressive cancer phenotypes of apoptosis resistance and enhanced cell invasion and migration compared with their non-CSC counterpart. Using gene manipulation strategies, we reveal for the first time that Cav-1 plays an essential role in CSC regulation and aggressiveness of SWCNT-transformed cells partly through p53 dysregulation. Overexpression of Cav-1 resulted in p53 inactivation, while its inhibition by shRNA activated the p53. The role of Cav-1 in tumorigenesis and metastasis of the transformed cells was evaluated in a xenograft mouse model using luciferase-labeled SWCNT-transformed cells. Our data demonstrate that Cav-1 not only promoted tumor formation but also metastasis of the transformed cells to neighboring tissues. Since CSCs are crucial to the initiation and early development of carcinogenesis, our findings on the induction of CSCs by SWCNTs and their regulation by Cav-1 could aid in the early detection and risk assessment of the disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56104 | GEO | 2015/03/05

SECONDARY ACCESSION(S): PRJNA242417

REPOSITORIES: GEO