Abstract
Extracellular vesicles (EVs) are released by nearly all cell types as part of normal cell physiology, transporting biological cargo, including nucleic acids and proteins, across the cell membrane. In pathological states such as cancer, EV-derived cargo may mirror the altered state of the cell of origin. Exosomes are the smaller, 50–150 nanometer-sized EVs released from fusion of multivesicular endosomes with the plasma membrane. Exosomes play important roles in cell-cell communication and participate in multiple cancer processes, including invasion and metastasis. Therefore, proteomic analysis of exosomes is a promising approach to discover potential cancer biomarkers, even though it is still at an early stage. Herein, we critically review the advances in exosome isolation methods and their compatibility with mass spectrometry (MS)-based proteomic analysis, as well as studies of exosomes in pathogenesis and progression of prostate and bladder cancer, two common urologic cancers whose incidence rates continue to rise annually. As urological tumors, both urine and blood samples are feasible for noninvasive or minimally invasive analysis. A better understanding of the biological cargo and functions of exosomes via high-throughput proteomics will help provide new insights into complex alterations in cancer and provide potential therapeutic targets and personalized treatment for patients.
Highlights
Extracellular vesicles (EV) comprise heterogeneous populations of membrane vesicles released by essentially all cell types
Exosomes are generated within an endosomal system as intraluminal vesicles (ILVs) and secreted during the fusion of multivesicular endosomes (MVEs) with the cell surface [2,3,4], whereas microvesicles are formed by an outward budding at the plasma membrane [5,6]
Exosomes are released from essentially all cell types and perform diverse cellular functions including intercellular communication, antigen presentation, and transfer of tumorigenic biomolecules
Summary
Extracellular vesicles (EV) comprise heterogeneous populations of membrane vesicles released by essentially all cell types They have different sizes ranging from 50–1000 nm in diameter and can be classified into two distinct categories: exosomes and microvesicles. Exosomes (50–150 nm) and microvesicles (50–1000 nm) differ in their modes of biogenesis, but they share common features, including biological processes (e.g., membrane-trafficking processes and cell adhesion) and biological cargo (e.g., membrane proteins, surface lipids, and nucleic acid) [1] (Table 1). We will discuss exosome isolation techniques for MS-based proteomic analysis and provide a summary of exosomal protein biomarker studies for PCa and BCa. is currently no analytical method that allows complete separation of exosomes from microvesicles [19] because of the overlapping size, similar morphology, and variable composition [20,21]. While performing debris needs to be separated (e.g., by low-speed centrifugation) and discarded before exosome isolation
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