Abstract 5763: Investigating the carcinogenic potential of various types of mineral fibers in the development of mesothelioma

Abstract

Abstract Malignant mesothelioma is a very aggressive tumor and has been linked to occupational and environmental exposure to carcinogenic mineral fibers such as asbestos. It was discovered recently that individuals carrying germline BAP1 mutations are predisposed to mesothelioma in presence of even minimal exposure to carcinogenic mineral fibers. Mesothelioma causes about 3,200 deaths per year in the U.S. and over 40,000 deaths per year worldwide. Most malignant mesothelioma studies have focused on carcinogenesis due to occupational exposure to the six regulated industrial mineral fibers collectively called ‘asbestos’. Besides this family of six regulated asbestos minerals, there are other non-regulated fibers that possess physical and chemical structures that are similar to industrial asbestos, and may also be carcinogenic. However, many of those mineral fibers are unknown for their carcinogenesis. We conducted serious studies on this topic and established in vitro and in vivo assays to help determine the carcinogenesis of various types of mineral fibers. We found that high mobility box 1 protein (HMGB1) is a key initiator of asbestos-induced inflammation, which plays critical roles in the development and growth of mesothelioma, and that HMGB1 may be a good indicator for fiber carcinogenesis and a biomarker for fibers exposure. Moreover, we found that specific immune system changes that occur after exposure to carcinogenic fibers, which may be a useful tool to help interrogate the carcinogenic potential of mineral fibers. In particular, the ability to induce an M2 macrophage response appears related to the potent tumor-inducing capacity of carcinogenic mineral fibers. Citation Format: David Larson, Mika Tanji, Andrea Napolitano, Sandra Pastorino, Michele Carbone, Haining Yang. Investigating the carcinogenic potential of various types of mineral fibers in the development of mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5763. doi:10.1158/1538-7445.AM2017-5763