Abstract
Extracellular Vesicles (EVs) have received considerable attention in recent years, both as mediators of intercellular communication pathways that lead to tumor progression, and as potential sources for discovery of novel cancer biomarkers. For many years, research on EVs has mainly investigated either the mechanism of biogenesis and cargo selection and incorporation, or the methods of EV isolation from available body fluids for biomarker discovery. Recent studies have highlighted the existence of different populations of cancer-derived EVs, with distinct molecular cargo, thus pointing to the possibility that the various EV populations might play diverse roles in cancer and that this does not happen randomly. However, data attributing cancer specific intercellular functions to given populations of EVs are still limited. A deeper functional, biochemical and molecular characterization of the various EV classes might identify more selective clinical markers, and significantly advance our knowledge of the pathogenesis and disease progression of many cancer types.
Highlights
Extracellular vesicles (EVs) are structures of variable size, surrounded by a lipid bilayer, which are released from any type of cell into the extracellular space and are detectable in body fluids
An analysis of the proteins most frequently identified in exosomes and deposited in the online EV databases ExoCarta, Vesiclepedia and EVPedia [21,22,23,24,25] highlights the presence of the tetraspanin family members CD9, CD63 and CD81, the small actin-binding protein Cofilin1, heat shock proteins such as Hsp70 and Hsp90, and enzymes involved in cell metabolism, including Enolase1, Aldolase A, phosphoglycerate kinase 1 (PGK1) and lactate dehydrogenase A (LDHA) [26]
Mass spectrometry analysis of fibroblast-derived exosomes indicates that these EVs stimulate migration and invasion of target cells and can play a role in metabolic reprogramming and extracellular acidification [66,67]. These findings indicate that EVs can be exchanged reciprocally between cancer cells and Cancer Associated Fibroblasts (CAFs), and that most of the biological changes that occur in either compartment as a result of cancer progression, including stemness, invasion, extracellular acidification, and metabolism reprogramming are mediated by specialized EVs
Summary
Extracellular vesicles (EVs) are structures of variable size (from 30 nm to a few μm), surrounded by a lipid bilayer, which are released from any type of cell into the extracellular space and are detectable in body fluids. The number of reports on cancer-derived EVs has surged, and it is well established that EVs contain functional proteins, microRNA, DNA, and mutated transcripts with oncogenic properties. It has been proposed by several studies that EV DNA may serve as a biomarker for cancer detection [11,12] and targeted therapy [13]. This very active field of investigation recently culminated in the demonstration that EVs can condition the pre-metastatic niche in vivo, a report that unequivocally corroborates active participation of EVs in cancer lethality [14]
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