Realization of Osteolysis, Angiogenesis, Immunosuppression, and Drug Resistance by Extracellular Vesicles: Roles of RNAs and Proteins in Their Cargoes and of Ectonucleotidases of the Immunosuppressive Adenosinergic Noncanonical Pathway in the Bone Marrow Niche of Multiple Myeloma
Abstract
Simple Summary
Abstract
1. Introduction
2. Ectoenzymes in the BMM
2.1. Expression Profiles of BMM Ectoenzymes in MM
2.2. Role of CD38 in Myeloma-Induced Osteoclastogenesis
2.3. Role of CD38 in Bioenergetic Plasticity in MM through Mitochondrial Transfer
3. The Immunosuppressive Role of Osteoclasts in the BMM
4. EVs
4.1. BM-MSC-Derived Exosomes Support Myeloma Cell Dissemination
4.2. BM Stromal Cell-Derived EVs Confer Resistance to PIs in Myeloma Cells
4.3. MSC-Derived Exosomes Confer Resistance to PIs in Myeloma Cells
4.4. MM-EVs Promote the Formation of New Bone Lesions
4.5. MM-EVs Promote Angiogenesis
4.6. MM-EVs Induce Immunosuppression in the BMM in MM
4.7. MM-Exos Transform MSCs into Cancer-Associated Fibroblasts (CAFs)
5. Conclusions
Funding
Conflicts of Interest
References
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Ex or EV Origin | Content | Mode of Alteration | Function | Ref. |
---|---|---|---|---|
BM-MSCs | Oncosuppressor miR-15a | ↓ | MM cell proliferation and dissemination | [20] |
IL-6, CCL2, fibronectin, junction plakoglobin/γ-catenin | ↑ | |||
p-FAK | ↓ | |||
BMSCs (murine 5T33 MM model) | unknown | ↑ | MM cell viability, proliferation, survival, and migration and bortezomib resistance | [21] |
BM-MSCs | PSMA3, PSMA3-AS1 | ↑ | PI resistance | [22] |
RPMI8226, OPM-2, LP-1, U266 | miR-146a | ↑ | Increase cytokine and chemokine secretion from MSCs | [13] |
CAG, RPMI8226 | heparanase | ↑ (bortezomib, carfilzomib, melphalan treatment) | Stimulate macrophage migration and secretion of TNF-α | [23] |
JJN3, H929, primary MM cells | IL-32 | ↑ | Promote OCL differentiation | [14] |
MM.1S | AREG (EGFR ligand) | ↑ | Osteolysis by promoting OCL differentiation and blocking osteogenic differentiation | [24] |
Murine MM cell 5TGM1 | DKK-1 | - | Osteolysis by promoting OCL differentiation and blocking osteoblast differentiation | [15] |
MM cells | lncRNA RUNX2-AS1 | ↑ | Reduce osteogenic differentiation | [16] |
RPMI8226, U266m ARH-77, primary MM cells | piRNA-823 | ↑ | Promote proliferation, tube formationm and invasion of ECs | [17] |
RPMI8226-HR | miR-135b | ↑ | Promote tube formation of ECs | [18] |
Murine MM cell 5T3MMvt, RPMI8226 | Angiogenin, VEGF, seepine1/PAI1, TIMP-1, | - | Promote angiogenesis, MDSC viability, and proliferation | [19] |
OPM-2 | miR-21 & miR-146a | ↑ | MSC proliferation, CAF transformation, and IL-6 secretion | [25] |
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Watanabe, T. Realization of Osteolysis, Angiogenesis, Immunosuppression, and Drug Resistance by Extracellular Vesicles: Roles of RNAs and Proteins in Their Cargoes and of Ectonucleotidases of the Immunosuppressive Adenosinergic Noncanonical Pathway in the Bone Marrow Niche of Multiple Myeloma. Cancers 2021, 13, 2969. https://doi.org/10.3390/cancers13122969
Watanabe T. Realization of Osteolysis, Angiogenesis, Immunosuppression, and Drug Resistance by Extracellular Vesicles: Roles of RNAs and Proteins in Their Cargoes and of Ectonucleotidases of the Immunosuppressive Adenosinergic Noncanonical Pathway in the Bone Marrow Niche of Multiple Myeloma. Cancers. 2021; 13(12):2969. https://doi.org/10.3390/cancers13122969
Chicago/Turabian StyleWatanabe, Takashi. 2021. "Realization of Osteolysis, Angiogenesis, Immunosuppression, and Drug Resistance by Extracellular Vesicles: Roles of RNAs and Proteins in Their Cargoes and of Ectonucleotidases of the Immunosuppressive Adenosinergic Noncanonical Pathway in the Bone Marrow Niche of Multiple Myeloma" Cancers 13, no. 12: 2969. https://doi.org/10.3390/cancers13122969
APA StyleWatanabe, T. (2021). Realization of Osteolysis, Angiogenesis, Immunosuppression, and Drug Resistance by Extracellular Vesicles: Roles of RNAs and Proteins in Their Cargoes and of Ectonucleotidases of the Immunosuppressive Adenosinergic Noncanonical Pathway in the Bone Marrow Niche of Multiple Myeloma. Cancers, 13(12), 2969. https://doi.org/10.3390/cancers13122969