The concept of “precision medicine,” an emerging approach using the genetic changes in a patient’s tumor to determine their disease treatment and prevention, can be seen as a new epoch in cancer management. Extracellular vesicles and exosomes are of high interest in the scientific community due to their role in intercellular communications. Especially the role of exosomes in cancer biology is an highly active area of investigation: They can be found in consistent concentrations in all body fluids, such as blood, salvia and urine (1–3), and promote the intercellular exchange of molecular information in physiological and pathological processes, such as inflammation and cancer (4–6).
Exosomes are membrane-derived vesicles with a size of 30–100 nm from endocytic origin. They transport a variety of functional molecules of nucleic acids including proteins, lipids, mRNA, miRNA and double-stranded DNA. Released by immune cells, exosomes may act as antigen-presenting vesicles, stimulate antitumoral immune responses or induce tolerogenic effects to suppress inflammation. Although exosome release is a normal process, increase in its rate and its differential cargo expressions are favorable for oncogenic progression and metastases. As exosomes can be collected from all types of biofluids, they represent the innovation of minimally or non-invasive liquid biopsy, and have the potential to reduce tumor biopsies. Especially in urologic cancers, such as bladder, kidney and/or prostate, urine is an important source of samples for biomarker research.
Urinary exosomes (UE) in cancer biology
Urinary exosomes are available in great quantity and represent each cell of the urinary tract, which makes them an important resource for recovery of biomarkers – a promising non-invasive diagnostic tool for renal diseases. UE can play a cell-signaling role, such as inducing the expression of aquaporin in recipient cells and therefore stimulate nephrogenesis (7) or can provide a source of biomarkers for cancer diagnosis if cell-type specific exosomes are found in urine. Especially for prostate cancer diagnosis, new biomarkers are needed to increase the specificity and sensitivity of possibilities for prostate cancer screenings and tests. Recent studies report that exosomes secreted from prostate cancer cells were found in urine collected after a prostate massage (8). miRNA expression in exosomes from prostate cancer patients was analyzed by next-generation sequencing. A huge difference of miRNA isoforms (isomiR-21, -2014 and -374) with 3’ modifications were found between control and affected men, which led to valuable diagnostic insights. Not only miRNA expression analysis, but also protein analysis by LC-MS/MS, indicated that not only exosome proteins and miRNA have a discriminative potential in prostate cancer, but also exosome lipids: especially the fatty acid binding protein 5 (FABP5) appeared to show high potential as a biomarker for prostate cancer. These are only a few examples that show how important urine could be as a tool for liquid biopsies, not only for prostate cancer but also for bladder cancer. The evidence that bladder cancer-derived exosomes indeed affect bladder cancer progression (9) and that lipid identification in urine exosomes can be envisioned as prostate cancer biomarkers, allows us to think about a way to use and target exosome excretion for the development of novel therapeutic treatment strategies specific for urinary tract cancers.
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- 2. Wang, D. and Sun W. (20149 Urinary extracellular microvesicles: isolation methods and prospects for urinary proteome. Proteomics 14: 1922–32.
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- 7. Quandt, D., et al. (2017) Implementing liquid biopsies into clinical decision making for cancer immunotherapy. Oncotarget 8: 48507–20.
- 8. Zijlstra, C. and Stoorvogel, W. (2016) Prostasomes as a source of diagnostic biomarkers for prostate cancer. J. Clin. Invest. 126: 1144–51.
- 9. Beckham, C.J. et al. (2014) Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression. J. Urol. 192: 583–92.