School of Medicine
Tumor microenvironment has been recognized as a key determinant of tumor formation and metastasis, but how tumor microenvironment is affected by nanomaterials is essentially unknown. Here, we investigated whether carbon nanotubes (CNTs), a widely used nanomaterial with known carcinogenic potential, can affect cancer-associated fibroblasts (CAFs), which are a key component of tumor microenvironment that provides necessary support for tumor growth. We show for the first time that single-walled CNT and to a lesser extent multi-walled and its COOH-functionalized form induced CAF-like cells, which are non-tumorigenic in animals, but promote tumor growth of human lung carcinoma and CNT-transformed lung epithelial cells. The mechanism by which CNT-induced CAF-like cells promote tumor growth involved the acquisition of cancer stem cells (CSCs) in cancer population. Gene knockdown experiments showed that an expression of podoplanin on CAF-like cells is essential for their effects, indicating the functional role of CAF-like cells and podoplanin in CNT tumorigenic process. Our findings unveil a novel mechanism of CNT-induced carcinogenesis through the induction of CAFlike cells that support CSCs and drive tumor formation. Our results also suggest the potential utility of podoplanin as a mechanism-based biomarker for rapid screening of carcinogenicity of CNTs and related nanomaterials for their safer design.
Digital Commons Citation
Luanpitpong, Sudjit; Wang, Liying; Castranova, Vincent; Dinu, Cerasela Zoica; Issaragrisil, Surapol; Yen, Yi Charlie; and Rojanasakul, Yon, "Induction Of Cancer-Associated Fibroblast-Like Cells By Carbon Nanotubes Dictates Its Tumorigenicity" (2016). Faculty & Staff Scholarship. 1517.
Luanpitpong, S., Wang, L., Castranova, V., Dinu, C. Z., Issaragrisil, S., Chen, Y. C., & Rojanasakul, Y. (2016). Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity. Scientific Reports, 6(1). https://doi.org/10.1038/srep39558