Salivary Extracellular Vesicle-Associated exRNA as Cancer Biomarker
Abstract
1. Introduction
2. EVs as Carriers of exRNA
3. EVs in Cancer Biology
4. Salivary EVs as Biomarkers
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Biological Effect | Mechanism of Action | Cell Source | Target | References |
---|---|---|---|---|
Resistance to chemotherapy | Transfer of MDR-1/P-gp | Docetaxel-resistant prostate cancer | Docetaxel-sensitive prostate cancer | [59] |
Transfer of miR-100, miR-222, miR-30a and miR-17 | Adriamycin and docetaxel-resistant breast cancer | Adriamycin and docetaxel-sensitive breast cancer | [60] | |
Transfer of miR-21 | Platinum-resistant ovarian cancer | Platinum-sensitive ovarian cancer | [61] | |
Transfer of miR-100-5p, miR-21 and miR-133b | Cisplatin-resistant lung cancer | Cisplatin-sensitive lung cancer | [62,63] | |
Transfer of miR-21, which downregulates APAF1 | Stroma | Ovarian cancer | [74] | |
Transfer of miR-146a with Snail mRNA | Cancer-Associated Fibroblasts | Pancreatic cancer | [73] | |
Activation of the antiviral/ NOTCH3 signaling pathway | Stroma | Breast cancer | [72] | |
Tumor immune-escape | Release of pro-inflammatory cytokines by macrophages, possibly mediated by miR-21 and miR-29a | Breast and lung cancer, melanoma | Tumor cells, fibroblasts, endothelial cells, and immune cells | [85,86,87] |
Inhibition of dendritic cell maturation and functions, by delivering specific miRNAs (e.g., miR-203, miR-212-3p) | Renal carcinoma, pancreatic cancer, melanoma | Dendritic and T cells | [87,88,89] | |
MDSCs activation, which leads to TGF-β-mediated suppression of T cell activity | Melanoma and colorectal carcinoma | CD14+ monocytes | [90,91] | |
Suppression of the T-cell activity mediated by PDL-1, TGF-β, Fas ligand and TRAIL | Melanoma, colorectal, gastric and prostate cancer, head and neck squamous cell carcinoma | CD8+T cells | [92,93,94,95,96] | |
Inhibition of NK cell cytotoxic activity, possibly mediated by MIC A ligand of NKG2D receptor | Mammary carcinoma, melanoma, cervical, head and neck, liver cancer | NK cells | [97,98,99] | |
Enhancement of immune response | Activation of a tumor antigen-specific immune response in humans | Melanoma and non-small cell lung cancer patients-derived dendritic cells | systemic administration | [100,101] |
Biological Effect | Mechanism of Action | Cell Source | Target | References |
---|---|---|---|---|
Tumor biomarkers | Transfer of miR-21, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-205 and miR-214 | Ovarian cancer | Serum | [102] |
Transfer of miR-17-3p, miR-21, miR-29a, miR-106a, miR-146 miR-155, miR-191, miR-192, miR-203, miR-205, miR-210, miR-212 and miR-214 | Lung cancer | Serum | [85,103] | |
Transfer of miR-18a, miR-221 and miR-224 | Hepatocellular carcinoma | Serum | [104] | |
Pro-angiogenic effect | Transfer of proangiogenic miRNAs, mostly regulated by HIF-1α (miR-155-5p, miR-210 and miR-494) | Melanoma, hepatocellular, lung and renal adenocarcinoma | CAFs and endothelial cells | [75,77,78,79,81] |
Decrease cell-to-cell adhesion | Reduction of E-cadherin, let-7i and β-catenin expression, and increase of Snail1-2, Twist1-2, Sip1, vimentin, ZEB2 and N-cadherin expression, activation of MAPK pathway | Breast and bladder cancer, melanoma | Mammary and urothelial cells epithelial cells, primary melanocytes | [67,68,69] |
Increase in cell migration/invasion | Lipids and proteins (e.g., CD81)-dependent stimulation of the cancer cell motility via Wnt signaling | Cancer Associated Fibroblasts | Melanoma, breast and prostate cancer | [70,71] |
Development of premetastatic niche | Delivery of TYRP2, VLA4, HSP70, an HSP90 isoform and the MET oncoprotein | Melanoma | Bone marrow progenitor cell | [83] |
Exosomal expression of tumor-specific integrin patterns | Osteosarcoma, rhabdomyosarcoma, Wilms tumor, skin and uveal melanoma, breast, colorectal, pancreatic and gastric cancer | Brain, lung and liver epithelium | [82] | |
Delivery of MIF | Pancreatic ductal adenocarcinoma | Kupffer cell | [80] | |
Delivery of specific oncogenic miRNAs, e.g., miR-125b, miR-130b and miR-155, which induce a neoplastic reprogramming of recipient cells | Prostate, renal cancer | Adipose-derived stem cells, lung epithelium | [81,84] |
Disease | Isolation Method | EV Biomarkers | Type of Biomarker | References |
---|---|---|---|---|
Brain injury and neurological disorders | Differential ultracentrifugation | CDC2, CSNK1A1, and CTSD | mRNA | [117] |
XYCQ EV Enrichment KIT | α-synuclein | protein | [119] | |
Oral squamous cell carcinoma | Differential ultracentrifugation | CD63 | protein | [126,127] |
Differential ultracentrifugation | PPIA | protein | [128] | |
Charge-based precipitation | miR-412-3p, miR-512-3p, miR-27a-3p, miR-494-3p, miR-302b-3p, miR-517b-3p | miRNA | [129] | |
Lung cancer | Affinity chromatography column combined with filter system (ACCF) | Annexin A1, A2, A3, A5, A6, A11; NPRL2; CEACAM1; MUC1; PROM1; HIST1H4A; TNFAIP3 | protein | [130] |
Affinity chromatography column combined with filter system (ACCF) | BPIFA1, CRNN, MUC5B, IQGAP | protein | [131] | |
Head and neck carcinoma | Differential ultracentrifugation | miR-486-5p, miR-486-3p, miR-10b-5p, miR-122 | miRNA | [132] |
Pancreatic cancer | Total Exosome Isolation Reagent (Invitrogen) | miR-1246, miR-4644 | miRNA | [133] |
Differential ultracentrifugation | Apbb1ip, Aspn, BCO31781, Daf2, Foxp1, Gng2, Incenp | mRNA | [134] |
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Chiabotto, G.; Gai, C.; Deregibus, M.C.; Camussi, G. Salivary Extracellular Vesicle-Associated exRNA as Cancer Biomarker. Cancers 2019, 11, 891. https://doi.org/10.3390/cancers11070891
Chiabotto G, Gai C, Deregibus MC, Camussi G. Salivary Extracellular Vesicle-Associated exRNA as Cancer Biomarker. Cancers. 2019; 11(7):891. https://doi.org/10.3390/cancers11070891
Chicago/Turabian StyleChiabotto, Giulia, Chiara Gai, Maria Chiara Deregibus, and Giovanni Camussi. 2019. "Salivary Extracellular Vesicle-Associated exRNA as Cancer Biomarker" Cancers 11, no. 7: 891. https://doi.org/10.3390/cancers11070891
APA StyleChiabotto, G., Gai, C., Deregibus, M. C., & Camussi, G. (2019). Salivary Extracellular Vesicle-Associated exRNA as Cancer Biomarker. Cancers, 11(7), 891. https://doi.org/10.3390/cancers11070891