Towards Understanding the Role of the Glycosylation of Proteins Present in Extracellular Vesicles in Urinary Tract Diseases: Contributions to Cancer and Beyond.

Extracellular vesicles (EVs) are a population of nanoscale particles surrounded by a phospholipid bilayer, enabling intercellular transfer of bioactive molecules. Once released from the parental cell, EVs can be found in most biological fluids in the human body and can be isolated from them. For this reason, EVs have significant diagnostic potential and can serve as an excellent source of circulating disease biomarkers. Protein glycosylation plays a key role in many biological processes, and aberrant glycosylation is a hallmark of various diseases. EVs have been shown to carry multiple glycoproteins, but little is known about the specific biological roles of these glycoproteins in the context of EVs. Moreover, specific changes in EV glycosylation have been described for several diseases, including cancers and metabolic, cardiovascular, neurological or kidney diseases. Urine is the richest source of EVs, providing almost unlimited (in terms of volume) opportunities for non-invasive EV isolation. Recent studies have also revealed a pathological link between urinary EV glycosylation and urological cancers, as well as other pathologies of the urinary tract. In this review, we discuss recent research advances in this field and the diagnostic/prognostic potential of urinary EV glycosylation. In addition, we summarize common methods for isolating EVs from urine and techniques used to study their glycosylation.