Extracellular vesicles: A dive into their role in the tumor microenvironment and cancer progression

Abstract

Extracellular vesicles (EVs) encompass a diverse set of membrane-derived particles released from cells and are found in numerous biological matrices and the extracellular space. Specific classes of EVs include apoptotic bodies, exosomes, and microvesicles, which vary in their size, origin, membrane protein expression, and interior cargo. EVs provide a mechanism for shuttling cargo between cells, which can influence cell physiology by transporting proteins, DNA, and RNA. EVs are an abundant component of the tumor microenvironment (TME) and are proposed to drive tumor growth and progression by communicating between fibroblasts, macrophages, and tumor cells in the TME. The cargo, source, and type of EV influences the pro- or anti-tumoral role of these molecules. Therefore, robust EV isolation and characterization techniques are required to ensure accurate elucidation of their association with disease. Here, we summarize different EV subclasses, methods for EV isolation and characterization, and a selection of current clinical trials studying EVs. We also review key studies exploring the role and impact of EVs in the TME, including how EVs mediate intercellular communication, drive cancer progression, and remodel the TME.

Isolation of Extracellular Vesicles of Holothuria (Sea Cucumber Eupentacta fraudatrix)

“…First, we tried to isolate EVs from the extract of the whole holothurian body using a combination of centrifugation and ultracentrifugation, this method is considered “a gold standard” for exosome isolation [ 1 , 5 , 27 ]. The obtained samples (sample I), were negatively stained and examined in TEM ( Figure 2 ).…”

“…Taking into account the array of data on the role of EVs in the implementation of life processes in the mammalian body, the need to study holothurian EVs is obvious. To isolate EVs, we applied a routine combination of centrifugation and ultracentrifugation method followed by gel filtration, which provided successful isolation and purification of exosomes from various mammalian liquid and organ samples [ 1 , 5 , 14 , 27 ]. However, when using this approach on whole extracts of holothurians, it was not possible to obtain preparations containing a noticeable amount of vesicles, which indicated an insufficient concentration of ES in the primary suspension.…”

“…The importance of extracellular vesicles (EVs), including exosomes, in mammalian organisms is undoubted, although discussions about the molecular mechanisms of their functioning, molecular composition, and isolation methods will obviously continue for many years to come. The efficient transmission of molecular signals from cell to cell is considered a fundamentally important function of EVs [ 1 , 2 , 3 , 4 , 5 ]. The universality of the established functions of EVs in the implementation of various processes in mammalian cellular systems encourages the study of EVs in organisms at other evolutionary levels, in particular, marine invertebrates.…”

“…The exosomes were isolated from various mammalian biological fluids, including urine, blood, breast milk, saliva, tears, and amniotic fluid [ 1 , 11 , 12 , 13 , 14 , 15 ]. Molecules of mRNA, microRNA, proteins, and lipids were found in exosomes, which gave reason to suggest that exosomes are involved in intercellular communications: their components can be transferred to recipient cells, affecting their functions [ 4 , 5 , 8 , 9 , 16 ].…”

“…The most widely used method for exosome isolation is a combination of centrifugation and ultracentrifugation, and numerous varieties of this approach have been published [ 1 , 2 , 5 , 25 , 26 , 27 ]; however, all the preparation results contain, along with exosomes, more or less different impurities. For example, a study of more than 200 preparations of various biological fluids by transmission electron microscopy (TEM) using specific antibodies to CD63 and CD9 (exosome markers), revealed “typical” exosomes, structureless impurities and spherical particles of low electron density (20–100 nm) without a boundary membrane (“non-vesicles”) in each preparation [ 14 ].…”