Exosomes and communication between tumours and the immune system: are all exosomes equal?

Abstract

Communication between cells is particularly important during tumour progression. Communication can take place through direct cell-cell interactions, but also through extracellular secretion of mediators acting at a distance. These mediators can be either soluble molecules or more complex structures called membrane vesicles, enclosing soluble factors within a lipid bilayer. A variety of extracellular membrane vesicles have been described, for instance microvesicles, ectosomes and a subtype called exosomes. The role of exosomes in tumour progression has been studied extensively in the last 10 years. In the present mini-review, we discuss our recent results, first showing the heterogeneity of the vesicles called exosomes and the probable existence of subpopulations of these exosomes, and secondly demonstrating that in vivo secretion of exosomes by some tumours can promote tumour progression, but that such a function cannot be generalized to all tumours and all exosomes.

Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells

“…Third, while we detect double-stranded DNA in EVs that possess exosomal-like characteristics and may be present in standard exosomal preparations, formation of DNA-containing EVs likely represents a distinct process [11]. Thus, further studies are warranted to elucidate the biogenesis, activity and clinical utility of DNA-containing EVs in cancer.…”

“…While EVs we describe possess some features of exosomes, their biogenesis and nomenclature are complex and controversial [11]. Thus far, we ruled out the involvement of TP53 and ASMase in vesicular emission of oncogenic DNA [24,26], but additional mechanisms are being investigated.…”

“…Among multiple subsets of EVs [11], those emanating from the plasma membrane are often larger, sedimented at lower centrifugal forces (P2/P3) and dependent on ASMase activity [24]. In contrast, smaller exosomal-like EVs are formed within endosomes, sediment at higher centrifugal forces (P4) and may be regulated by p53 [26].…”

“…The mechanisms of packaging and vesicular emission of proteins and nucleic acids are poorly understood and controversial [11]. Processes of membrane blebbing and protein clustering on the cell surface have been previously implicated [11,12], including in the release of larger EVs (100-1,000nm) known as ectosomes, microvesicles or large oncosomes [5].…”

“…Processes of membrane blebbing and protein clustering on the cell surface have been previously implicated [11,12], including in the release of larger EVs (100-1,000nm) known as ectosomes, microvesicles or large oncosomes [5]. Alternatively, endocytosis of membrane receptors and their interactions with subcellular vesicle trafficking pathways may result in formation of small EVs (50-100nm) known as exosomes [7,11,13].…”