Abstract 4562: Slug knockdown suppresses malignant phenotype of nanomaterial-transformed human lung epithelial cells

Abstract

Abstract Nanomaterials have increasingly become part of modern everyday life, but their long-term health effects are largely unknown. Previous studies have shown that carbon nanotubes (CNTs), one of the most widely used nanomaterials in industry, can induce or promote tumor formation in animals, but the underlying mechanisms are unclear. We previously found that chronic exposure to CNTs induced malignant transformation of human lung epithelial cells, the primary cellular target of inhaled nanomaterials. The transformed cells exhibited aggressive cancer phenotypes, including increased cell migration, invasion and anchorage-independent cell growth. We hypothesized that such increased aggressiveness may be due to epithelial-mesenchymal transition (EMT). To test this hypothesis, cultured human lung epithelial BEAS-2B cells were continuously exposed to physiologically relevant concentration (0.02 μg/cm2 surface area dose) of single-walled CNT (SWCNT) for a period of 6 months. The cells were then analyzed for EMT markers and aggressive cellular behavior. Western blot analysis of EMT markers indicated an increased expression of mesenchymal markers and decreased epithelial markers, indicating the activation of EMT in the chronic SWCNT-exposed cells. Moreover, the cells exhibited a dramatic increase in one of the EMT master regulators, a transcription factor Slug (Snail2). We hypothesized that Slug upregulation may be responsible for the aggressive phenotype of the cells. We stably downregulated the Slug expression using lentiviral shRNA particles, and examined its effect on cell migration and invasion by Transwell® assays. Our results showed that knockdown of Slug attenuated cell migration and invasion without having any effect on cell proliferation. Together, our results indicated the activation of EMT by SWCNT and demonstrated its role in aggressive cancer phenotype. Slug plays a crucial role in this process and could serve as a potential biomarker for CNT-induced malignancies. Citation Format: Maria Voronkova, Sudjit Luanpitpong, Liying Wang, Yon Rojanasakul. Slug knockdown suppresses malignant phenotype of nanomaterial-transformed human lung epithelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4562. doi:10.1158/1538-7445.AM2015-4562