Yon Rojanasakul
Professor and Leader of the Sara and James Allen Comprehensive Lung Cancer Program at West Virginia University Cancer Institute, USA.
Title: Nanomaterial carcinogenicity: Role of cancer stem cells and tumor microenvironment
Biography
Biography: Yon Rojanasakul
Abstract
Nanomaterial carcinogenicity: Role of cancer stem cells and tumor microenvironment
Tumor Microenvironment (TME) has been recognized as a key determinant of tumorigenesis and metastasis, but how TME is affected by nanomaterials is largely unknown. We demonstrated that certain nanomaterials including Carbon Nanotubes (CNTs) can affect TME by activating Cancer-Associated Fibroblasts (CAFs) to promote tumor growth and metastasis of human lung cancer cells. This effect of CNTs is dependent on the physicochemical characteristics of CNTs such as tube wall number and surface reactivity and functionalization. Single-walled CNTs and to a lesser extent multi-walled CNTs and their COOH-functionalized forms strongly induce CAFs, which was shown to promote tumor formation of preexisting human lung cancer cells and CNT-transformed lung epithelial cells. The mechanism by which CNT-induced CAFs promote tumor growth involves acquisition of Cancer Stem Cells (CSCs) in the TME, which drives tumor growth and metastasis. Gene knockdown experiments showed that an expression of podoplanin on CAFs is essential for the tumor-promoting and CSC-inducing effects of CNTs. Together our findings indicate a novel role of TME in promoting CNT-induced carcinogenesis through the activation of podoplanin-associated CAFs that support CSC expansion and tumor growth. Our results also suggest the potential utility of podoplanin as a mechanism-based biomarker for CNT-induced malignancies.