Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles
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Valentina R. Minciacchi1, Sungyong You1, Cristiana Spinelli1, Samantha Morley2, Mandana Zandian1, Paul-Joseph Aspuria3, Lorenzo Cavallini1,4, Chiara Ciardiello1,5, Mariana Reis Sobreiro1, Matteo Morello1, Geetanjali Kharmate6, Su Chul Jang7, Dae-Kyum Kim7, Elham Hosseini-Beheshti6, Emma Tomlinson Guns6, Martin Gleave6, Yong Song Gho7, Suresh Mathivanan8, Wei Yang1, Michael R. Freeman1,2 and Dolores Di Vizio1,2
1 Division of Cancer Biology and Therapeutics, Departments of Surgery, Biomedical Sciences and Pathology and Laboratory Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
2 The Urological Diseases Research Center, Boston Children’s Hospital, Boston, MA, Department of Surgery, Harvard Medical School, Boston, MA, USA
3 Women’s Cancer Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
4 Department of Experimental and Clinical Biomedical Science, University of Florence, Florence, Italy
5 Experimental Pharmacology Unit, Department of Research, IRCCS-Istituto Nazionale Tumori G. Pascale, Naples, Italy
6 Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, BC, Canada
7 Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
8 Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia
Dolores Di Vizio, email:
Keywords: Extracellular Vesicles, SILAC Proteomics, Cancer metabolism, Tumor progression, Amoeboid blebbing
Received: January 05, 2015 Accepted: February 22, 2015 Published: March 14, 2015
Large oncosomes (LO) are atypically large (1-10µm diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease. We report that 25% of the proteins, identified by a quantitative proteomics analysis, are differentially represented in large and nano-sized EVs from prostate cancer cells. Proteins enriched in large EVs included enzymes involved in glucose, glutamine and amino acid metabolism, all metabolic processes relevant to cancer. Glutamine metabolism was altered in cancer cells exposed to large EVs, an effect that was not observed upon treatment with exosomes. Large EVs exhibited discrete buoyant densities in iodixanol (OptiPrepTM) gradients. Fluorescent microscopy of large EVs revealed an appearance consistent with LO morphology, indicating that these structures can be categorized as LO. Among the proteins enriched in LO, cytokeratin 18 (CK18) was one of the most abundant (within the top 5th percentile) and was used to develop an assay to detect LO in the circulation and tissues of mice and patients with prostate cancer. These observations indicate that LO represent a discrete EV type that may play a distinct role in tumor progression and that may be a source of cancer-specific markers.
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