Abstract

Potential Role of Exosomes in the Development of Malignant Mesothelioma

Phillip Munson, Researcher, University of Vermont

Malignant mesothelioma (MM) is a fatal cancer of mesothelial cells attributed to asbestos exposure. MM has a long latency period of 20 to 50 years after initial exposure. Inhaled asbestos first encounters lung epithelial cells or macrophages which attempt to clear the fibers. However, little is known about how asbestos fibers are capable of eliciting a devastating cancer of the mesothelium, which is present at distant locations to the initial assault. Exosomes are intercellular messengers capable of conferring a vast array of signaling between cells that is essential in both normal physiology and disease states, particularly cancer. We hypothesize a role of exosomes in the development of MM with the prediction that asbestos exposed epithelial cells convey a tumorigenic message to mesothelial cells via exosomes, thus leading to the initiation and progression of MM. We intend to characterize exosomes, and their cargo, from normal and asbestos exposed epithelial cells as well as study the effects, and in vivo localization, of these exosomes on possible target mesothelial cells and tissues. Preliminary findings suggest candidate biomarkers in asbestos-exposed epithelial cell derived exosomes and potential target sites of localization in mouse models. Supported by grants from the NIH (ES021110) and the DoD (W81XWH-14-1-0199).