Uncovering the Diagnostic Power of Extracellular Vesicles

Since their discovery 3 decades ago, the role of extracellular vesicles in various diseases has been studied intensely, but how they might serve as diagnostic biomarkers remains poorly understood. Recent technological advances in proteomics and genomics have given scientists new insights into the composition and function of these vesicles. In this morning’s scientific session, “Plasma Microvesicles: A Treasure Trove of Novel Biomarkers for Disease Diagnosis,” three experts will delve into the evolving knowledge about these intriguing particles.
Secreted by living cells, extracellular vesicles contain proteins, nucleic acids, and other components specific to the cell of origin. They can be derived from different cellular compartments and are generally classified based on size, with exosomes having a diameter of less than 150 nm and larger vesicles measuring up to 1000 nm in diameter.
Extracellular vesicles promote cell-to-cell communication, making it not unexpected that they are present in multiple biological fluids including peripheral blood, urine, and cerebrospinal fluid. Recent studies suggest that the shedding of extracellular vesicles is a highly regulated process that occurs in a spectrum of cell types, particularly in tumor cells.
During the session, Alex J. Rai, PhD, will highlight the role of extracellular vesicles and their cargo in cancer diagnostics. Recent work has shown that these vesicles are potential contributors to oncogenesis, tumor growth, metastasis, and drug resistance. Rai will focus on the diagnostic and prognostic utility of extracellular vesicles in prostate cancer and uveal melanoma. The controversy surrounding PSA screening in healthy men as a biomarker for prostate cancer illustrates the potential for overdiagnosis and overtreatment. Prostate cancer is therefore an excellent example of how proteins in extracellular vesicles could provide an accurate diagnosis, identify individuals with aggressive disease, and guide treatment selection.
Uveal melanoma is a rare, highly aggressive eye cancer in which nearly 50% of patients die from liver metastasis. Rai will describe the potential prognostic value of markers found in extracellular vesicles as predictors of uveal melanoma progression to metastatic disease.
Richard Sweet, MD, will explain the role of circulating microvesicles in sepsis, which remains highly lethal and challenging to diagnose early or treat. The prospects for using microvesicles in septic patients range from rapid diagnostics to guiding individualized therapy. In sepsis, circulating microvesicles are more abundant and have characteristic phenotypic profiles, which seem to play key roles in multi-organ dysfunction and septic shock. In his talk, Sweet will highlight the promising role of inducible nitric oxide synthase in circulating microvesicles as a biomarker of the onset of sepsis.
Alan Wu, PhD, will discuss the potential role of troponin detected in circulating microvesicles as a novel marker of reversible myocardial ischemia. Work by other groups has shown that circulating cardiac extracellular vesicles abundantly contain cardiac-specific microRNAs that indicate cardiac damage and have diagnostic potential as biomarkers of acute myocardial infarction.
Attendees will walk away with a clear understanding of the composition, function, and potential diagnostic role of circulating microvesicles in cancer, sepsis, and cardiovascular disease. They will also become familiar with the techniques currently available to isolate and characterize microvesicles and the technical and biological challenges that may hinder their wide use as biomarkers, including their low concentration in circulation and the lack of standardized methods to analyze them.