Adipose Tissue-Derived Extracellular Vesicles and the Tumor Microenvironment: Revisiting the Hallmarks of Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. EVs
AT-EVs and Their Role in the Tumor Microenvironment
3. AT-EVs and the Hallmarks of Cancer
3.1. Resisting Cell Death
3.2. Sustaining Proliferative Signaling
3.3. Inducing Angiogenesis
3.4. Activation of Invasion and Metastasis
3.5. Dysregulation of Cellular Energetics
3.6. Enabling of Replication Immortality
3.7. Evading Growth Suppressors, Gene Instability, and Mutation
3.8. Avoiding Immune Destruction and Inflammation
4. Dual Roles of AT-EVs in Tumor Cells: miRNAs
5. Perspectives on Immune Cells
5.1. Tumor-Associated Neutrophil Polarization to N1 Phenotype
5.2. Lymphocytes
6. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Resisting Cell Death | |||
---|---|---|---|
Type of Vesicle | Content | Effect | References |
ADMSC-Exos | N.D. | Protect breast cancer from apoptosis | [47] |
ATM-Exos | miR-155 | Resistance to cell death in breast cancer cells via caspase-3, Bcl-2, APAR-1, FADD, and RIP1 | [50] |
AT-Exos | Decreased levels of miR-148b | Decrease apoptosis in breast cancer cells | [21] |
Sustaining Proliferative Signaling | |||
Type of vesicle | Content | Effect | References |
AT-Exos | N.D. | Tumor progression by reprogramming surrounding cells/ Increases proliferation and invasion/ Increase angiogenesis | [54] |
BCC-EVs | miR-144 miR-126 miR-155 | Increased lipolysis in adipocytes tissue toward CAA phenotype | [56] |
AD-Exos | N.D. | Increased MMP-3 in lung cancer cells | [54] |
CAA-Exos | miR-21 | Suppressed ovarian cancer cells apoptosis and increased chemoresistance by targeting APAF-1 | [129] |
AT-Exos (obese AT) | circ-DB RNAs | Growth of hepatocarcinoma by targeting USP-7 deubiquitination | [129] |
ADMSC-Exos | N.D. | Increased proliferation of osteosarcoma cells via induction of COLGALT2 | [39] |
AT-EVs (obese AT) | N.D. | Increased CREB phosphorylation in ZR75.1 breast cancer cells | [55] |
AD-Exos | miR-23 | Increased cell growth of hepatocarcinoma cells | [124] |
AT-EVs (obese AT) | N.D. | Increased proliferation of MCF-7 breast cancer cells via ERK phosphorylation | [15] |
Inducing Angiogenesis | |||
Type of Vesicle | Content | Effect | References |
ADMSC-EVs | IL-8 CCL2 VEGF-D | Increased migration and tube-like formation in endothelial cells | [66] |
ADMSC-Exos treated with VEGF-C | miR-132 | Lymphangiogenesis via TGF-β/Smad signaling | [67] |
ADMSC-Exos | miR-31 | Increased migration and tube-like formation in (HUVEC) endothelial cells | [70] |
Activating Invasion and Metastasis | |||
Type of Vesicle | Content | Effect | References |
ADMSC-EVs from diabetic subjects | EGFR-1/IL-6 | Increased migration and metastasis of breast cancer cells via EGFR-1/IL-6 activating JAK/STAT-3 pathway | [73] |
AT-EVs (obese AT) | MMP-9 | Increased invasive capacity of MDA-MB-231 breast cancer cells | [15] |
AD-Exos (from differentiated 3T3-L1) | MMP-3 | Increased invasive capacity of 3LL lung tumor cells | [74] |
AD-EVs | N.D. | Tumor progression in melanoma, lung, and breast cancer | [39] |
AD-Exos | N.D. | Increase in melanoma cell migration and invasion; tumor progression in melanoma and prostate cancer by upregulating genes involved in fatty acid oxidation | [75] |
ADMSC-Exos | N.D. | Increased migration of MCF-7 cells by through the upregulation of Wnt- signaling pathway | [57] |
ADMSC-Exos | N.D. | Increased migration, invasion, and epithelial-mesenchymal transition of MCF-7 cells by TGF-β/Smad and PI3K/AKT signaling pathways crosstalk | [76] |
CAA-Exos | N.D. | Exchange of enzymes implicated in fatty acid oxidation triggering melanoma cells migration. | [45] |
AT-EVs (obese AT) | N.D. | Increased migratory capacity in MDA-MB-231 breast cancer cells via PI3K/AKT signaling pathway | [15] |
AD-Exos | miR-23 | Increased migration in HCC cells through VHL/HIF-1α axis | [126] |
Dysregulation of Cellular Energetics | |||
Type of Vesicle | Content | Effect | References |
AD-Exos | Hydroxyacyl-coenzyme A dehydrogenase (HCDH) | Improving lipid metabolism, respiratory chain activity, and tumor migration in melanoma cells | [75] |
AD-Exos | Mitochondrial fission protein 1 (FIS-1) Mitochondrial dynamin like GTPase (OPA-1) | Induce mitochondrial redistribution to the edge of melanoma cells favoring migration | [45] |
AD-Exos | Trifunctional enzyme (ECHA) | Increased fatty acid oxidation in melanoma cells | [45] |
Evading Growth Suppressors | |||
Type of Vesicle | Content | Effect | References |
ADMSC-Exos | N.D. | Breast cancer cell growth via activation of YAP and TAZ downstream Hippo signaling pathway | [47] |
Gene Instability and Mutation | |||
Type of Vesicle | Content | Effect | References |
ATM-Exos | miR-155 | Inhibited p53 in MCF-7 cells | [51] |
AD-Exos | SOX-9 | Induced tumorigenesis in MFC-10 epithelial cells | [93] |
Avoiding Immune Destruction and Inflammation | |||
Type of Vesicle | Content | Effect | References |
ADMSC-Exos | N.D. | Inactivation of T cells | [110] |
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Moraes, J.A.; Encarnação, C.; Franco, V.A.; Xavier Botelho, L.G.; Rodrigues, G.P.; Ramos-Andrade, I.; Barja-Fidalgo, C.; Renovato-Martins, M. Adipose Tissue-Derived Extracellular Vesicles and the Tumor Microenvironment: Revisiting the Hallmarks of Cancer. Cancers 2021, 13, 3328. https://doi.org/10.3390/cancers13133328
Moraes JA, Encarnação C, Franco VA, Xavier Botelho LG, Rodrigues GP, Ramos-Andrade I, Barja-Fidalgo C, Renovato-Martins M. Adipose Tissue-Derived Extracellular Vesicles and the Tumor Microenvironment: Revisiting the Hallmarks of Cancer. Cancers. 2021; 13(13):3328. https://doi.org/10.3390/cancers13133328
Chicago/Turabian StyleMoraes, João Alfredo, Carol Encarnação, Victor Aguiar Franco, Luiz Gabriel Xavier Botelho, Gabriella Pacheco Rodrigues, Isadora Ramos-Andrade, Christina Barja-Fidalgo, and Mariana Renovato-Martins. 2021. "Adipose Tissue-Derived Extracellular Vesicles and the Tumor Microenvironment: Revisiting the Hallmarks of Cancer" Cancers 13, no. 13: 3328. https://doi.org/10.3390/cancers13133328