From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research
Abstract
:Simple Summary
Abstract
1. Introduction
2. Mechanisms of Exosome Biogenesis
2.1. Endosome Formation
2.2. MVB Formation and Cargo Encapsulation
2.3. Cargo Sorting to MVBs
2.4. Extracellular Release
3. Mechanisms of Exosome Absorption
3.1. Exosome Transport and Targeting to Recipient Cells
3.2. Interaction with Recipient Cells and Internalization
3.3. Fate of Internalized Exosomes
4. Relevance of Exosome Secretion and Uptake in Cancer and Cancer Therapy
4.1. Regulation of Exosome Secretion in Cancer
4.2. The Role of Exosome Targeting in Cancer and Drug Delivery
4.3. Cancer Exosomes as a Therapeutic Target
5. Challenges and Perspectives for Designing Studies on Exosome Biology
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Steps | Pathways | Mechanisms | References |
---|---|---|---|
Exosome biogenesis | |||
Endosome formation | Clathrin-mediated endocytosis | FCHO, AP2, adaptor proteins, Dynamin, HSC70, auxilin | [20] |
Caveolin-dependent endocytosis | Caveolin-1 | [21] | |
Clathrin- and caveolin-independent endocytosis | CLIC/GEEC; ARF6; Actin | [20,21] | |
MVB formation | ESCRT-dependent pathway | ESCRT-0/I/II/III, VPS4 | [22,23,24] |
Non-canonical ESCRT-dependent pathways | Syndecan-Syntenin-Alix, heparinase; HD-PTP | [25,28,29,30,31] | |
ESCRT-independent pathway | LC3, nSMase2, ceramide; cholesterol, caveolin-1, flotillins; TSPNs (CD63, TSPN6, CD9, CD81) | [34,35,36,37,38] [39,40,41,42,43] [45,46,47,48,49,50,51] | |
Cargo sorting | Protein-sorting pathways | ESCRT or ESCRT-independent pathways; Rab coupling protein | [25,26,27,32,33,53,54] |
DNA-sorting pathways | TSPN interaction with micronuclei; PINK1 | [56,58] | |
RNA-sorting pathways | nSMase2, SP/NK1R, RBPs, ESCRT-II, Alix; LLPS, 3′ end adenylation or uridylation | [5,59,60,61,62,63,64,65,66,67,68] [69,70,71,72] | |
Extracellular release | SNARE-mediated membrane fusion | Fas/Fap-1/caveolin-1, lncRNA HOTAIR | [74,75] |
Actin reorganization | Cortactin, Arp2/3, Rab27a, Coronin1b; Rab25, Fascin | [76,77,78,79] | |
Microtubule-mediated transport | Rab7, RILP; Rab31, Arl8b/SKIP/HOPS, Rab7 GAPs (TBC1D2B, TBC1D15), Rab7 GEFs (Mon1a/b, NEDD8-Coro1a); ISG15 | [80,81,82] [83,84,85,86] [87] | |
Rab-regulated trafficking and fusion | Rab27a/b, Rab27 GEFs (MADD, FAM45A), KIBRA, Slp4, Munc13-4; Rab11; Rab35, Ca2+ | [88,89,90,91,92,93] [94,95,96,97] |
Steps | Factors/Processes | Mechanisms | References |
---|---|---|---|
Exosome absorption | |||
Exosome biodistribution and organ-specific accumulation | Retention in lymph nodes and bone | Exosome size | [14] |
Route of administration | Intratumoral, intravenous, etc. | [99,100,101] | |
Cell type-specific rate of exosome uptake | Cell type-dependent factors | [102] | |
Targeting to recipient cell | Receptor–ligand interaction | RVG, SDF-1; integrins (αvβ5, α6β4, α6β1, α4β7), TSPNs (TSPAN8, CD63), CD47 | [103,104,105] [112,113,114,115,116] |
Lipid targeting | Phosphatidylethanolamine, sphingomyelin | [106,107] | |
Cell-type-specific exosome uptake | Recognition moieties from the donor cell type | [108,109,110,111] | |
Recipient cell interactions | Signal transduction via receptors | MHC-peptide complex, TNF receptors | [118,119] |
Membrane fusion | Rabs, SNARE; membrane rigidity and lipid content | [107,122] | |
Clathrin-mediated endocytosis | Dynamin-2; transferrin | [117,124,125] | |
Lipid raft endocytosis | Cholesterol, sphingolipid, flotillin | [126,127,128,129] | |
Macropinocytosis | Rac1 GTPase, actin, cholesterol, EGFR | [130,131,132] | |
Caveolin-dependent endocytosis | Caveolin-1 | [133,134] | |
Phagocytosis | PI3K, phosphatidylserine | [125,135,136,137,138] | |
Internalized exosomes | Lysosomal degradation | Trafficking to lysosomes (e.g., Rab7) | [80,139] |
Bypassing lysosomal degradation | Passive diffusion; cargo activation by acidification; RNA transfer to ER; fusion with endosomal membrane (e.g., LBPA) | [108,140,141,142,143] | |
Re-release | Sorting to recycling endosomes | [144,145] |
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Lau, N.C.H.; Yam, J.W.P. From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research. Cancers 2023, 15, 1992. https://doi.org/10.3390/cancers15071992
Lau NCH, Yam JWP. From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research. Cancers. 2023; 15(7):1992. https://doi.org/10.3390/cancers15071992
Chicago/Turabian StyleLau, Nicolas Cheuk Hang, and Judy Wai Ping Yam. 2023. "From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research" Cancers 15, no. 7: 1992. https://doi.org/10.3390/cancers15071992
APA StyleLau, N. C. H., & Yam, J. W. P. (2023). From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research. Cancers, 15(7), 1992. https://doi.org/10.3390/cancers15071992