Table 1.
Factors stimulating EV release.
| Mechanism of induction of EV release | EV size (nm) | EV source | EV content | References |
|---|---|---|---|---|
| EXOSOMES AND EXOSOME-LIKE VESICLES/EXTRACELLULAR VESICLES | ||||
| • Tumor necrosis factor (TNF) | 20–50 | Human bronchial epithelial cells | TNF-R1, TRADD | (69) |
| • Inhibition of oncogenic Epidermal Growth Factor Receptor Kinase | 30–100 | Human cancer cell lines | EGFR, P-EGFR, & exo-gDNA | (70) |
| • Heparanase | 30–120 | Human myeloma cell line | Syndecan-1, VEGF & HGF | (71) |
| • Hypoxia | 30–100 | Human breast cancer lines | Elevated miR-210 | (72) |
| • Plasma membrane depolarization | 40–100 | Neurones and astrocytes | Cell adhesion and membrane proteins | (73, 74) |
| • Cross-linking of CD3 • (TCR activation) |
50–100 | Jurkat T cells or T lymphoblasts | CD3/TCR, CD2, LFA-1, MHC-I and II, & CXCR4 | (75) |
| • Glutamate | 50–100 | Oligodendrocytes in the brain | Cre-recombinase | (4) |
| • Induction of the oncogene Wnt5A | ND | Melanoma cell line | IL-6 & the pro-angiogenic factors IL-8, VEGF & MMP2 | (76) |
| • Activation of Her2 by ligands EGF and Heregulin | ND | Her2 overexpressing breast cancer cells (BT-474) | Activated Her2 | (77) |
| • GAIP interacting protein C • Terminus (GIPC) depletion |
40–100 | Pancreatic cancer cell line | Overexpression of drug resistance gene ABCG2 | (78) |
| EXOSOMES AND MICROVESICLES (MVs) | ||||
| • Increasing intracellular Ca2+ by: • Thrombin receptor activation via • α-thrombin or thrombin-receptor • Activating peptide (TRAP) |
Exo: 40–100 MV:100–1000 |
Platelets from human whole blood | Exosomes: CD63 MV: Integrin & P-selectin |
(64) |
| EXOSOMES AND GIANT MULTIVESICULAR BODIES (MVB) | ||||
| • Increased intracellular Ca2+: Monensin ionophore & activation of transferrin receptor |
60–100 | Human erythro-leukemia cell line | ND | (79, 80) |
| INTRALUMENAL VESICLES | ||||
| • Increasing intracellular Ca2+:
Calcium containing media |
60–80 | Mice bone marrow-derived mast cells | MHC-II | (81) |
| MVs AND APOPTOTIC VESICLES | ||||
| • Increasing intracellular Ca2+:
P2X7 activation via ATP |
250–2000 | Microglia | Pro-IL-1β | (82) |
| MICROVESICLES (MVs) | ||||
| • Increasing intracellular Ca2+: 1. P2X7-R activation by ATP |
<0.5 μm | THP-1 monocytes | Bioactive IL-1β | (83) |
| 2. ATP-mediated activation of P2X7R |
ND | RAW MØ | Intracellular isoform of IL-1ra | (84) |
| 3. Activation of PAK1/2 via Cdc42 & Rac1-dependent pathways by thrombin receptor-activating & collagen or calcium ionophore | <1.0–1.5 μm | Platelets | Cortactin, filamin A and actin | (85) |
| • Hypoxia and gamma radiation | <1 μm | MVs- Human & murine lung cancer cell lines | ND | (86) |
| • Elevated peptidylarginine deiminases (PAD2 & PAD4) induced by BzATP stimulation of P2X7 receptors |
200 nm average | Prostate cancer cell line | ND | (87) |
| • EGF Treatment (activation of Rho & ROCK) |
≤0.22 μm | Human cervical HeLa cells | ND | (88) |
| • Phorbol 12-myristate 13-acetate (PMA) |
≤1 μm | Human cancer cell lines | HLA Class- I, CD29, CD44v7/8, CD51, chemokine receptors CCR6 & CX3CR1, extracellular matrix metalloproteinase inducer (EMMPRIN), epithelial cell adhesion molecule (EpCAM) | (89) |
| • Activation of P2X7 via ATP | 0.5–1 μm | Macrophages | Phospholipids | (90) |
| • Respiratory Infections (LPS, live H. influenzae bacteria or viral mimetic Poly:IC) |
20–1000 nm 100–400 nm |
Broncho alveolar lavage fluid (BALF) from mice | ND | (91) |
| MICROVESICLES (MVs) OR MICROPARTICLES (MPs) | ||||
| Overexpression of v-H-RAS | ND | Melanoma cells | MMP-2 | (92) |
| MICROPARTICLES (MPs) | ||||
| • Thrombin induced activation of Rho & ROCK-II pathway | <1 um | Human microvascular endothelial cell line | ND | (93) |
| • Combination of ionizing radiation & TNF (stimulation of ROS) | <1 um | Human umbilical vein endothelial cells | Tissue Factor (TF) | (94) |
| • Activation of acid A-SMase by benzoyl-ATP | 100 nm−1 μm | Glial cells | A-SMase | (95) |
| EXTRACELLULAR VESICLES (EVs) | ||||
| • Sub-lethal photodynamic treatment, cytotoxic insult | 300–400 nm | Human prostatic cancer cells in vitro and in in vivo in mouse | Apoptotic markers, drugs from their parent cells, tumor membrane & endosome contents | (63) |
| • Activation by LPS | 0.1–5 μm | Dendritic cells | ND | (96) |
| GESICLES | ||||
| • Overexpression of VSVglycoprotein | 100 nm | Human kidney and lung cell lines | VSV-G | (32) |
| ONCOSOMES | ||||
| • Activation of EGFR & AKT Pathways |
0.5–5 μm | Prostate cancer cells | Caveolin-1 | (20) |
| • Silencing of the cytoskeletal regulator diaphanous-related formin-3 (DIAPH3) by ERK | >1 μm | Prostate cancer cell line (DU145) | miR-125a | (97) |
ND, Not defined.