Exosomes: A Common Pathway for a Specialized Function

Abstract

Exosomes are membrane vesicles that are released by cells upon fusion of multivesicular bodies with the plasma membrane. Their molecular composition reflects their origin in endosomes as intraluminal vesicles. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins linked to cell type-associated functions. Exosome secretion participates in the eradication of obsolete proteins but several findings, essentially in the immune system, indicate that exosomes constitute a potential mode of intercellular communication. Release of exosomes by tumor cells and their implication in the propagation of unconventional pathogens such as prions suggests their participation in pathological situations. These findings open up new therapeutic and diagnostic strategies.

Tumour-released exosomes and their implications in cancer immunity

“…However, an alternative novel mechanism that is now emerging involves the active release by tumour cells of immune suppressive membrane microvesicles, also known as exosomes. 24 Microvesicles or exosomes are endosome-derived organelles of 50-100 nm size, which are actively secreted through an exocytosis pathway that is used under normal as well as pathological conditions for receptor discharge and intercellular cross-talk [24][25][26] (Figure 1). Even though exosomes have recently been found to be released by virtually all cell types, most of the studies are actually focused on exosomes secreted by reticulocytes, immune cells and tumour cells.…”

“…Even though exosomes have recently been found to be released by virtually all cell types, most of the studies are actually focused on exosomes secreted by reticulocytes, immune cells and tumour cells. 24 Proteomic analysis of microvesicles underlined that although several molecules are shared between microvesicles of different cell origin, exosome functionality seems to be determined by specific protein content. In fact, exosomes derived from DCs (also called DEX) can elicit T cell activation in mouse model when previously loaded with tumour peptides, thanks to a set of co-stimulatory and cell adhesion molecules as well as functional MHC class II and class I molecules.…”

“…49 Altogether, these features make tumour-released exosomes an efficient platform for the in vivo transfer of cross-talk signals. As a matter of fact, the large array of bioactive molecules incorporated into tumour-produced exosomes 24,35,36 prompts speculation that these organelles might potentially play a paracrine role in shaping host environment. A scheme of the hypothetical pathways involving tumour exosomes is depicted in Figure 3.…”

Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis

“…An important function of tumor cell-generated MVs is to evade host immunity. 39 TCMVs have diameters in the size range of 30-100 nm, 39 and are generated by fusion of endosomal membranes (eg, from multivesicular bodies 87 ) with the plasma membrane, which then exfoliates PM-derived MVs with various functions, including suppression of antitumor cell immunity 39 ( Table 2). TCMVs also promote tissue invasion by transport and release of proteases, which digest host tissues at the site of invasion.…”

Circulating TNFR1 exosome-like vesicles partition with the LDL fraction of human plasma

“…Exosomes are small membrane-enclosed vesicles, 30-to 200-nm in diameter, that correspond to the internal vesicles of endolysosome-related multivesicular bodies and are released from the cell via exocytic fusion with the plasma membrane [3][4][5]. Exosomes can interact with target cells to mediate regulatory functions in an acellular fashion, as well as facilitate the transfer of integral membrane proteins, as well as mRNAs and microRNAs [6]. Exosomes mediate several important biological functions, including antigen presentation, T cell co-stimulation, and apoptosis.…”