A Comprehensive Picture of Extracellular Vesicles and Their Contents. Molecular Transfer to Cancer Cells

Abstract

Critical processes such as growth, invasion, and metastasis of cancer cells are sustained via bidirectional cell-to-cell communication in tissue complex environments. Such communication involves the secretion of soluble factors by stromal cells and/or cancer cells within the tumor microenvironment (TME). Both stromal and cancer cells have been shown to export bilayer nanoparticles: encapsulated regulatory molecules that contribute to cell-to-cell communication. These nanoparticles are known as extracellular vesicles (EVs) being classified into exosomes, microvesicles, and apoptotic bodies. EVs carry a vast repertoire of molecules such as oncoproteins and oncopeptides, DNA fragments from parental to target cells, RNA species (mRNAs, microRNAs, and long non-coding RNA), and lipids, initiating phenotypic changes in TME. According to their specific cargo, EVs have crucial roles in several early and late processes associated with tumor development and metastasis. Emerging evidence suggests that EVs are being investigated for their implication in early cancer detection, monitoring cancer progression and chemotherapeutic response, and more relevant, the development of novel targeted therapeutics. In this study, we provide a comprehensive understanding of the biophysical properties and physiological functions of EVs, their implications in TME, and highlight the applicability of EVs for the development of cancer diagnostics and therapeutics.

Inhibition of a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

“…CD63 and Alix are among the proteins mostly identified on exosomes. CD63 is a tetraspanin widely explored as exosome marker, as is expressed in various late endocytic organelles [64,65], while Alix works as an auxiliary component for the ESCRT machinery during ILVs formation [66,67]. Alix also binds to the cytosolic adaptor syntenin, which in turns connects to the transmembrane proteins syndecans and supports EV biogenesis [68].…”

Tiny Actors in the Big Cellular World: Extracellular Vesicles Playing Critical Roles in Cancer

“…Microvesicles are involved in several key functions, including intercellular communication, signal transduction, and immune regulation. In particular, these entities mediate tumor invasion, inflammation, metastases, stem-cell renewal, and expansion [ 25 ]. During biogenesis, microvesicles receive important structural components, including Flotillin-2, Annexin V, integrins, selectin, CD40, and metalloproteinase [ 26 ].…”

“…In contrast, exosomes are between 30–100 nm in size, and are generated using the endosomal pathway [ 25 ]. Exosome biogenesis begins with the formation of early endosomes that undergo inward (or reverse) budding and then subsequent formation of intraluminal vesicles (ILVs), and referred to as multivesicular bodies (MVBs) or late endosomes.…”

“…Exosome biogenesis begins with the formation of early endosomes that undergo inward (or reverse) budding and then subsequent formation of intraluminal vesicles (ILVs), and referred to as multivesicular bodies (MVBs) or late endosomes. As a final step, late endosomes may either directly fuse with lysosomes, wherein the endocytosed cargo is degraded, or they may fuse with the plasmalemma releasing its ILVs (exosomes) to the extracellular space [ 25 , 27 ]. ESCRT (endosomal sorting complexes required for transport) is a molecular complex that plays an important role in MVB formation and regulation ( Figure 1 ).…”

Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications

“…There is a growing body of literature concerning molecules that EVs may transfer, which includes: nucleic acids, enzymes, proteins, other signalling molecules and immunogenic materials. Given the focus of this review is engineering methods to augment the therapeutic potential of EVs, further information on the extensive cargo of these nanoparticles may be found elsewhere [ 5 , 6 , 7 ].…”