Abstract 3892: Unique pleural vs peritoneal mesothelioma exosomal signature: does mesothelial cell susceptibility to asbestos matter

Abstract Malignant mesothelioma (MM) is a cancer of mesothelial cells of the pleura or peritoneum caused exclusively by asbestos exposure. It is a deadly cancer which is only diagnosed at terminal stages, possibly due to the long latency period of development and lack of biomarkers for early diagnosis. Both pleural and peritoneal mesothelial cells can develop MM in response to asbestos, however, pleural MM (85%) is more common than peritoneal MM (15%). To get an insight of this difference we first isolated exosomes from pleural (Hmeso, H2373) and peritoneal (ORT) MM cells and performed proteomic analysis. We found that 45 proteins are common and specific to MM cells derived from pleural cavity (Hmeso/H2373) while 86 proteins are specific to ORT cells lines derived from peritoneal cavity. On the other hand, the non-transformed mesothelial cell line, LP9, showed a completely different profile with 269 proteins secreted in exosomes not shared with MM models. This led us to hypothesize that mesothelial cells of two different locations may have different susceptibility to asbestos, accounting for differences observed in pleural and peritoneal MM. To test this hypothesis we exposed human primary pleural and peritoneal mesothelial cells to asbestos for 8 h, and performed massively parallel sequencing on the RNA. Gene expression analysis performed on the RNA-Seq data showed a higher magnitude of responses from pleural mesothelial cells as compared to peritoneal mesothelial cells for the same genes. In addition, at a p<0.05 and 2-fold threshold, unique genes expressed in pleural mesothelium were pro-inflammatory genes known to be involved in MM tumorigenesis. Taken together, results from our study suggest that exosomal cargo from pleural and peritoneal MM cells bear unique signatures which may be due to the different responses of pleural and peritoneal mesothelial cells to asbestos. Future directions involve assessing miRNA cargo from exosomes of pleural and peritoneal MM cells and identifying potential biomarker candidates. This work is supported by grants from NIH (RO1 ES021110), DoD (W81XWH-14-1-0199) and the University of Vermont Cancer Center/Lake Champlain Cancer Research Organization. Citation Format: Arti Shukla, Phillip Munson, Joyce K. Thompson, Julie Dragon, Maximilian B. MacPherson, Hector Peinado. Unique pleural vs peritoneal mesothelioma exosomal signature: does mesothelial cell susceptibility to asbestos matter. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3892.