Role of Caveolin-1 in Carbon Nanotube-Induced Stem-Like Cells and Tumorigenesis

S. Luanpitpong, L. Wang, V. Castranova, T. Stueckle, Y. Rojanasakul
West Virginia University, US

Keywords: carbon nanotubes, stem-like cells, tumorigenesis, caveolin-1


Carbon nanotubes (CNT) hold great promise to create new and better products, but their long-term adverse health effects are a major concern. The objective of this study was to develop an in vitro model for lung cancer risk assessment of CNT and to evaluate the in vivo tumorigenicity of chronic CNT-exposed human lung cells. We demonstrated the induction of CSC-like cells, a potential driving force of tumor initiation and progression, from human lung epithelial cells by chronic exposure to SWCNT, as evaluated by tumor spheres side population. These CSC-like cells, which express a high level of Cav-1, displayed increased cell migration and invasion, compared with their non-CSC counterpart. Overexpression of Cav-1 further promoted the CSC induction, cell motility, and in vivo tumorigenesis. Our findings provide novel evidence for the induction of CSC-like cells by chronic SWCNT exposure, which are likely a driving force of SWCNT tumorigenesis, and demonstrated a positive regulatory role of Cav-1. We suggest that detection of CSC may provide a valuable tool for early detection of CNT carcinogenesis and that Cav-1 might serve as a biomarker or drug target for CNT tumorigenesis.