Abstract
Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates. Proteins included established EV markers, and vesicular trafficking proteins such as Rab GTPases and tetraspanins. Differentially-expressed proteins offer potential for cancer diagnosis and prognosis. Network analysis of vesicle quantity and proteomes identified EV components associated with vesicle secretion, including CD81, CD63, syntenin-1, VAMP3, Rab GTPases, and integrins. Integration of vesicle proteomes with whole-cell molecular profiles revealed similarities, suggesting EVs provide a reliable reflection of their progenitor cell content, and are therefore excellent indicators of disease.
Highlights
Extracellular vesicles (EVs) represent a diverse population of communication pods released from cells
To characterize and compare extracellular vesicle proteomes, EVs were harvested from 60 cell lines (NCI60)
It has become clear that extracellular vesicles are an important component of cellular communication informing fields including cancer biology, immunology, and virology
Summary
Extracellular vesicles (EVs) represent a diverse population of communication pods released from cells. Ranging in size from 40 to 1000 nm, EVs include exosomes, microvesicles, and apoptotic bodies. Exosomes are described as 40-150 nm endocyticallyderived vesicles formed by intraluminal budding of multivesicular bodies (MVBs) which are released following MVB fusion with the plasma membrane. Microvesicles are generally larger than exosomes, and are shed by budding and fission events directly at the cell membrane. Apoptotic bodies are formed by plasma membrane blebbing, and can contain packaged organelles following initiation of cell death. Further sub-populations of vesicles likely exist, reflecting the heterogeneity of cellular biology encapsulated by EVs
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