Year: 2018
Type: article
Abstract: Rationale: 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.Methods: Exosomes isolated from three pancreatic cancer (PC) cell lines displaying variable gemcitabine (GEM) resistance (PANC-1, MIA PaCa-2, and BxPC-3) were tested for their capacity to transmit chemoresistance among these cell lines.Comparative proteomics was performed to identify key exosomal proteins that conferred chemoresistance.Cell survival was assessed in GEM responsive PC cell lines treated with recombinant Ephrin type-A receptor 2 (EphA2), a candidate chemoresistance transfer factor, or exosomes from a chemoresistant PC cell line treated with or without EphA2 shRNA.Results: Exosomes from chemoresistant PANC-1 cells increased the 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.Conclusion: Exosomal EphA2 expression could transmit chemoresistance and may potentially 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.
Source: Theranostics
DOI: 10.7150/thno.26650
Authors: Jia Fan, Qian Wei, Eugene J Koay, Yang Liu, Bo Ning, Paul W Bernard, Ning Zhang, Haiyong Han, Matthew H Katz, Zhen Zhao, Ye Hu
Institutions: Arizona State University, Tianjin Medical University Cancer Institute and Hospital, The University of Texas MD Anderson Cancer Center, Tianjin Medical University, Houston Methodist, Houston Methodist Research Institute, Translational Genomics Research Institute, National Institutes of Health, National Institutes of Health Clinical Center, Weill Cornell Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,671
Awards: G1802197572, Real-time Detection of Active TB in HIV Exposed Children on CustomizedNanotrap, G3765401515, Quantification of Circulating Antigens for Pediatric TB Diagnosis andTreatment Monitoring, Detecting pathogen and host factors on extracellular vesicles for pediatric TB diagnosis and management, Exosome-based microRNA biomarkers for Non-invasive and Early Detection of Pancreatic Cancer, SPORE in Lymphoma
OpenAlex ID: W2902466936