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

Valentina R. Minciacchi, Sungyong You, Cristiana Spinelli, Samantha Morley, Mandana Zandian, Paul Joseph Aspuria, Lorenzo Cavallini, Chiara Ciardiello, Mariana Reis Sobreiro, Matteo Morello, Geetanjali Kharmate, Su Chul Jang, Dae Kyum Kim, Elham Hosseini-Beheshti, Emma Tomlinson Guns, Martin Gleave, Yong Song Gho, Suresh Mathivanan, Wei Yang, Michael R. FreemanDolores Di Vizio

Research output: Contribution to journalArticle

Abstract

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 nanosized 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.

Original languageEnglish
Pages (from-to)11327-11341
Number of pages15
JournalOncotarget
Volume6
Issue number13
Publication statusPublished - 2015

Keywords

  • Amoeboid blebbing
  • Cancer metabolism
  • Extracellular vesicles
  • SILAC proteomics
  • Tumor progression

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles'. Together they form a unique fingerprint.

  • Cite this

    Minciacchi, V. R., You, S., Spinelli, C., Morley, S., Zandian, M., Aspuria, P. J., Cavallini, L., Ciardiello, C., Sobreiro, M. R., Morello, M., Kharmate, G., Jang, S. C., Kim, D. K., Hosseini-Beheshti, E., Guns, E. T., Gleave, M., Gho, Y. S., Mathivanan, S., Yang, W., ... Di Vizio, D. (2015). Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles. Oncotarget, 6(13), 11327-11341.