Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles

摘要: // Valentina R. Minciacchi 1 , Sungyong You Cristiana Spinelli Samantha Morley 2 Mandana Zandian Paul-Joseph Aspuria 3 Lorenzo Cavallini 1,4 Chiara Ciardiello 1,5 Mariana Reis Sobreiro Matteo Morello Geetanjali Kharmate 6 Su Chul Jang 7 Dae-Kyum Kim Elham Hosseini-Beheshti Emma Tomlinson Guns Martin Gleave Yong Song Gho Suresh Mathivanan 8 Wei Yang Michael Freeman 1,2 and Dolores Di Vizio Division of Cancer Biology Therapeutics, Departments Surgery, Biomedical Sciences Pathology Laboratory Medicine, Samuel Oschin Comprehensive Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA The Urological Diseases Research Boston Children’s Hospital, Boston, MA, Department Harvard School, Women’s Program, 4 Experimental Clinical Science, University Florence, Italy 5 Pharmacology Unit, Research, IRCCS-Istituto Nazionale Tumori G. Pascale, Naples, Vancouver Prostate Centre, Urologic Sciences, British Columbia, BC, Canada Life Pohang Science Technology, Pohang, Republic Korea Biochemistry, La Trobe Institute for Molecular University, Bundoora, Australia Correspondence to: Vizio, email: Keywords : Extracellular Vesicles, SILAC Proteomics, metabolism, Tumor progression, Amoeboid blebbing Received January 05, 2015 Accepted February 22, Published March 14, Abstract Large oncosomes (LO) are atypically large (1-10µm diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding membrane blebs associated with advanced disease. We report that 25% proteins, identified by a quantitative proteomics analysis, differentially represented in nano-sized EVs prostate cancer cells. Proteins enriched included enzymes involved glucose, glutamine amino acid all metabolic processes relevant to cancer. Glutamine metabolism was altered cells exposed EVs, an effect not observed upon treatment exosomes. exhibited discrete buoyant densities iodixanol (OptiPrep TM ) gradients. Fluorescent microscopy revealed appearance consistent LO morphology, indicating these structures can be categorized as LO. Among proteins LO, cytokeratin 18 (CK18) one most abundant (within top th percentile) used develop assay detect circulation tissues mice patients These observations indicate represent EV type may play distinct role tumor progression source cancer-specific markers.