Hallmarks of Exosomes

Figures & data

Figure 1. The various biological fluids in the human body.

Figure 2. The exosome's structure.

Exosomes contain DNA, RNA, proteins, lipids and metabolites. Exosomes are composed of various proteins: transmembrane proteins such as tetraspanins, antigen presenting molecules, glycoproteins and adhesion molecules; proteins in exosome lumen such as heat shock proteins (Hsp), cytoskeletal proteins, ESCRT components, membrane transport, fusion proteins, growth factors and cytokines. Exosomes also comprise of multiple lipids such as cholesterol, ceramides, sphingomyelin, phosphatidylinostol (PI), phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and gangliosides (GM) along with nucleic acids such as mRNA, miRNA, non-coding RNA and DNA in their lumen.

ESCRT: Endosomal sorting complex required for transport; FasL: Fas ligand; Hsc: Heat shock cognate; TfR: Transferrin receptor; TGF: Transforming growth factor; TNF: Tumor necrosis factor; TRAIL: TNF-related apoptosis-inducing ligand; TSG: Tumor suspectibility gene.

Figure 3. The biogenesis of exosomes and release pathway.

(A) The exosome is derived from early plasma membrane-formed endosomes (endocytosis). (B) Further, early endosomes are transformed into late endosomes. (C) After that, it forms early multivesicular bodies. (D) Multivesicular bodies of the late stage. (E) In order to release exosomes, late multivesicular bodies may either be joined with autophagosomes and follow the degradation pathway through lysosomes or they can be fused to the plasma membrane via the microtubules and cytoskeletal network, and be released by budding from the cytoplasmic membrane (exocytosis).

Figure 4. Hallmarks of exosomes.

Table 1. Clinical use of tumor-derived exosome as diagnostic or prognostic biomarkers.

Clinical use	Used sample	Exosomes				Ref.
Diagnostic	Plasma Serum Urine	miR-19-3p miR-629 miR-151a-5p miR-21-5p miR-181a-5p CD151 miR-23a miR-196a-3p	miR-23a-3p miR-205-5p miR-17-3p miR-486-5p let-7d-3p CD171 miR-155 miR-501-3p	miR-361-5p miR-200b miR-361-5p miR-320b miR-30d-5p LRG1 miR-126	miR-200b-5p miR-100 miR-15b-5p miR-30a-3p miR-210-3p tetraspanin8 miR-205	[33,58,61,62,142,145–152]
Prognostic	Plasma Serum	miR-4257 miR-23b-3p miR-23a EGFR miR-21	miR-10b-5p miR-21-5p miR-32 GRB2 miR-146a-5p	miR-208a miR-96 miR-425-3p HSP70 miR-155	miR-222-3p miR-221-3p miR-18a NY-ESO-1	[142,144,153–157]
Therapy	Plasma Serum	miR-221-3p miR-146a-5p	miR-29a miR-150	miR-634		[136,143]

EGFR: Epidermal growth factor receptor; GRB2: Growth factor receptor-bound protein 2; HSP70: Heat shock protein 70; LRG1: Leucine rich alpha-2-glycoprotein 1; NY-ESO-1: Cancer-testis antigen NY-ESO-1.

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