Exosomes in the Diagnosis and Treatment of Renal Cell Cancer
Abstract
:1. Introduction
2. Methods
3. Composition, Secretion, and Detection of Exosomes
3.1. Composition of Exosomes
3.2. Secretion of Exosomes
3.3. Detection of Exosomes
4. The Contribution of Exosomes to RCC
4.1. TME
4.2. Angiogenesis
4.3. Immune Escape
4.4. Cancer Cell Invasion and Metastasis
5. The Role of Exosomes in the Diagnosis of RCC
5.1. mRNA
5.2. miRNA
5.3. lncRNAs and circRNAs
6. Exosomes in the Treatment of RCC
6.1. Tumour Drug Resistance
6.2. Tumour Vaccines
7. Conclusions and Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Size | 30–100 nm | |
Formation and release | Formed intracellularly within multivesicular bodies | |
Isolation and detection | Ultracentrifugation, electron microscopy, western blotting, mass spectrometry, and nanoparticle tracking analysis | |
Proteins | Type | Cargo |
Tetraspanin | CD9, CD63, CD81 | |
Heat shock protein | Hsp70, Hsp90 | |
Membrane transport and fusion proteins | Rab, Annexins (I, II, IV, V, VI) | |
Antigen presentation | MCH I, MCH II | |
Adhesion molecules | Integrins, ICAM-1, CD146 | |
Lipid raft | LAPA, Flotillin-1, Cholesterol | |
Cytoskeletal proteins | ||
Lipids | Cholesterol, ceramide, phosphatidylserine, phosphatidylinositol, phosphatidylcholine, sphingomyelin, ganglioside | |
Nucleic acids | DNA, mRNA, miRNA, lncRNA, circRNA |
Type | EV Source | EV Cargoes | Analysis Method | Cohorts | Clinical Significance | Ref. |
---|---|---|---|---|---|---|
mRNA | Supernatants | VEGF, FGF2, ANGPT1, EFNA3, MMP2, and MMP9 | Microarray, qRT-PCR | Cancer stem cells | mRNAs implicated in tumor progression and metastasis through molecular characterization of VEGF, FGF2, ANGPT1, EFNA3, MMP2, and MMP9. | [76] |
Urine | GSTA1, CEBPA, and PCBD1 genes | Microarray, qRT-PCR | 46 RCC patients (33 with ccRCC), 22 HS | Significantly lower in ccRCC patients compared with HS. Increased to normal level 1 month after nephrectomy. | [130] | |
miRNA | Supernatants | miR-200c, miR-650 | Microarray, qRT-PCR | Cancer stem cells | miR-200c and miR-650 significantly upregulated in CD105+ microvesicles. | [76] |
miR-100, miR-296 | miR-100 and miR-296 significantly downregulated. | |||||
miR-29a, miR-650, miR-151 | miR-29a, miR-650, and miR-151 are associated with tumor invasion and metastasis. | |||||
miR-549a | qRT-PCR | 786-O cell, 786-O-SR cell | Lower in TKI-resistant cells and exosomes. | [89] | ||
miR-205 | qRT-PCR | HK-2 cell, 786-O cell | Significant differences in concentration between the two cell lines. | [142] | ||
Urine/Supernatants | miR-204-5p | qRT-PCR | Mouse and human tRCC cell lines | Significantly increased in primary RCC cell lines established from transgenic mouse tumors and tumor tissue from 2 Xp11 tRCC patients. | [143] | |
Urine | miR-126-3p | Microarray, qRT-PCR | 81 ccRCC patients, 33 HS | Differentiated ccRCC patients from HS | [144] | |
miR-126-3p combined miR-449a | ||||||
miR-126-3p combined miR-34b-5p | Differentiated patients with ccRCC and small renal masses (pT1a, ≤4 cm) from HS. | |||||
miR-126-3p combined miR-486-5p | 24 benign renal tumor patients, 33 HS | Differentiated benign patients from HS. | ||||
miR-30c-5p | RNA sequencing, qRT-PCR | 70 early-stage ccRCC patients, 30 HS | Significantly lower in early-stage ccRCC patients compared with HS. | [78] | ||
Plasma | miR-92a-1-5p, miR-149-3p, miR-424-3p | RNA sequencing, qRT-PCR | 5 RCC, 5 healthy controls. 22 RCC, 16 healthy controls | Significantly downregulated in the plasma exosomes of RCC. | [132] | |
miR-15a | Microarray, qRT-PCR | ACHN cell | Upregulated in ccRCC cells. BTG2 gene is negatively correlated with miR-15a expression. | [123] | ||
miR-let-7i-5p, miR-26a-1-3p, miR-615-3p | RNA-sequencing, qRT-PCR | A cohort of 44 metastatic RCC patients for screening and 65 validation controls | Low levels correlated with poor OS of metastatic RCC patients. | [145] | ||
Serum | miR-1233, miR-210 | qRT-PCR | 82 ccRCC patients, 80 HS | Significantly higher in ccRCC patients than in HS | [131] | |
miR-210 | Microarray, qRT-PCR | 45 pre-operative and 35 post-operative ccRCC patients, 30 HS | Significantly higher in ccRCC patients compared with HS, Significantly higher in pre-operative than post-operative samples. | [84] | ||
miR-224 | qRT-PCR | 108 ccRCC patients | High levels are correlated with shorter PFS, CSS, and OS of ccRCC patients | [133] | ||
Protein | Urine | MMP9, CP, PODXL, CAIX, and DKK4 | LC-MS/MS, western blotting | 29 RCC, 23 healthy controls | MMP9, CP, PODXL, CAIX, and DKK4 are higher in patients with RCC compared with HS. | [146] |
CD10, EMMPRIN, DPEP1, syntenin 1, and AQP1 | CD10, EMMPRIN, DPEP1, syntenin 1, and AQP1 are higher in HS than in patients with RCC | |||||
Serum | CD103 | Flow cytometry | 76 metastatic and 133 non-metastatic ccRCC patients | Higher ratio of CD103+ EVs to total EVs in samples from metastatic patients compared with samples from non-metastatic patients. | [77] | |
Azurocidin | LC-MS/MS | 19 ccRCC patients, 10 HS | Significantly higher in ccRCC patients than in HS | [85] | ||
Tissue | Azurocidin | LC-MS/MS | 20 paired tumors and adjacent normal tissues from ccRCC patients | Significantly higher in ccRCC patients than in HS | [85] | |
Supernatants | RAB27B | ExoELISA-ULTRA CD63 kit | A498 cell | Oncogenic role in RCC and sunitinib resistance. | [110] | |
IncRNA | Plasma | Circulating lncARSR | qRT-PCR | 71 advanced ccRCC patients, 32 HS | Poor sunitinib response, Sunitinib resistance via competitively binding miR-34/miR-449. | [90] |
circRNA | Plasma | circ_400068 | CircRNA microarray | 28 RCC | Upregulated in RCC plasma exosomes, tissue samples, and cells. | [141] |
Lipid | Urine | LysoPE | microLC-Q-TOF-MS | 8 ccRCC patients, 8 HS | 48 differential lipidome expression (22 upregulated and 26 downregulated) in ccRCC. | [147] |
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Boussios, S.; Devo, P.; Goodall, I.C.A.; Sirlantzis, K.; Ghose, A.; Shinde, S.D.; Papadopoulos, V.; Sanchez, E.; Rassy, E.; Ovsepian, S.V. Exosomes in the Diagnosis and Treatment of Renal Cell Cancer. Int. J. Mol. Sci. 2023, 24, 14356. https://doi.org/10.3390/ijms241814356
Boussios S, Devo P, Goodall ICA, Sirlantzis K, Ghose A, Shinde SD, Papadopoulos V, Sanchez E, Rassy E, Ovsepian SV. Exosomes in the Diagnosis and Treatment of Renal Cell Cancer. International Journal of Molecular Sciences. 2023; 24(18):14356. https://doi.org/10.3390/ijms241814356
Chicago/Turabian StyleBoussios, Stergios, Perry Devo, Iain C. A. Goodall, Konstantinos Sirlantzis, Aruni Ghose, Sayali D. Shinde, Vasileios Papadopoulos, Elisabet Sanchez, Elie Rassy, and Saak V. Ovsepian. 2023. "Exosomes in the Diagnosis and Treatment of Renal Cell Cancer" International Journal of Molecular Sciences 24, no. 18: 14356. https://doi.org/10.3390/ijms241814356