Abstract 585: Exosomal EphA2 transmits chemoresistance and predicts pancreatic cancer patient responses to therapy

Abstract

Abstract Exosomes are small extracellular vesicles secreted by most cells that are found in blood and other bodily fluids, and which contain cytoplasmic material and membrane factors corresponding to their cell type of origin. Exosome membrane factors and contents have been reported to alter adjacent and distant cell behavior in multiple studies, but the impact of cancer-derived exosomes on chemoresistance is less clear. We therefore analyzed exosomes from the human pancreatic cancer (PC) cell lines PANC-1, MIA PaCa-2 and BxPC-3 for their ability to transmit chemoresistance, finding that PANC-1 exosomes increased the gembicitabine (GEM) resistance of MIA PaCa-2 and BxPC-3 cell cultures. Comparative proteomics determined that PANC-1 exosomes overexpressed Ephrin type-A receptor 2 (EphA2) versus exosomes of less chemoresistant PC cell lines MIA PaCa-2 and BxPC-3. EphA2-knockdown in PANC-1 cells inhibited their ability to transmit exosome-mediated chemoresistance to MIA PaCa-2 and BxPC-3, while treatment of MIA PaCa-2 and BxPC-3 cells with soluble EphA2 did not promote chemoresistance, indicating that membrane carried EphA2 was important for the EphA2 chemoresistance effect. EphA2 levels on circulating exosomes were markedly increased in mice bearing PANC-1 tumors and PC patients who subsequently revealed poor responses to treatment. We thus concluded that exosomal EphA2 expression could transmit chemoresistance and may serve as a minimally-invasive predictive biomarker for PC treatment response. Further work should address whether additional exosomal factors regulate resistance to other cancer therapeutic agents for PC or other cancer types. Citation Format: Jia Fan, Qian Wei, Eugene J. Koay, Yang Liu, Zhen Zhao, Ye Hu. Exosomal EphA2 transmits chemoresistance and predicts pancreatic cancer patient responses to therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 585.