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The emerging role of extracellular vesicles as biomarkers for urogenital cancers

Key Points

  • Extracellular vesicles are small (40–5,000 nm diameter) membrane-bound vesicles that can be categorized into exosomes, microvesicles and apoptotic bodies according to their size, origin, morphology and mode of release

  • Whereas the generation of exosomes involves endocytosis, formation of multivesicular bodies and subsequent membrane fusion, microvesicles are produced by membrane budding and apoptotic bodies result from membrane blebbing during apoptosis

  • Over the past 10 years, various methodologies for the effective isolation of extracellular vesicles have been developed, including centrifugation, affinity capture, precipitation and the use of microfluidic devices

  • Extracellular vesicle cargo is thought to reflect the cell-type of origin, suggesting it could be a promising source for the discovery of novel biomarkers

Abstract

The knowledge gained from comprehensive profiling projects that aim to define the complex genomic alterations present within cancers will undoubtedly improve our ability to detect and treat those diseases, but the influence of these resources on our understanding of basic cancer biology is still to be demonstrated. Extracellular vesicles have gained considerable attention in past years, both as mediators of intercellular signalling and as potential sources for the discovery of novel cancer biomarkers. In general, research on extracellular vesicles investigates either the basic mechanism of vesicle formation and cargo incorporation, or the isolation of vesicles from available body fluids for biomarker discovery. A deeper understanding of the cargo molecules present in extracellular vesicles obtained from patients with urogenital cancers, through high-throughput proteomics or genomics approaches, will aid in the identification of novel diagnostic and prognostic biomarkers, and can potentially lead to the discovery of new therapeutic targets.

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Figure 1: Classes of extracellular vesicles.
Figure 2: Extracellular vesicle biogenesis.
Figure 3: Multistep validation of biomarkers from extracellular vesicles.

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Acknowledgements

This work was supported by a Movember Discovery grant from Prostate Cancer Canada (D2013-21) and by the Canada Research Chair Program to T. Kislinger. M. Nawaz, F. Fatima and L. Neder acknowledge funding from FAPESP (Sao Paulo Research Foundation, Proc. No. 12/24574-3) and CAPES (Coordination for the Improvement of Higher Education Personnel). K. Ekström and X. Wang are supported by The Swedish Research Council (K2012-52X-09495-25-3), the BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, the Stiftelsen Handlanden Hjalmar Svensson Foundation and the Magnus Bergvalls Foundation. G. Camussi acknowledges funding from Associazione Italiana per la Ricerca sul Cancro (AIRC) IG2012 n. 12890.

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Nawaz, M., Camussi, G., Valadi, H. et al. The emerging role of extracellular vesicles as biomarkers for urogenital cancers. Nat Rev Urol 11, 688–701 (2014). https://doi.org/10.1038/nrurol.2014.301

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