Research progress of multiple myeloma cell-derived extracellular vesicles in clinical diagnosis and treatment
-
摘要: 多发性骨髓瘤(multiple myeloma，MM)细胞来源的细胞外囊泡(extracellular vesicles，EVs)通过转运特异性生物活性分子进行细胞间通信，参与血管生成、骨溶解、免疫抑制、耐药性等多个过程，因此可以作为有潜力的生物标志物辅助诊断和探索MM治疗的新方式。本文旨在综述其重塑骨髓微环境促进MM进展的机制、与耐药性的关系、作为生物标志物的研究进展、通过作为干扰通信的治疗靶点和工程化改造促进MM治疗的临床前景，分析得出特定MM-EVs的纯化表征、功能分析和安全性是MM-EVs临床转化的重要挑战。Abstract: Multiple myeloma cell-derived extracellular vesicles(MM-EVs) are involved in multiple myeloma related processes such as angiogenesis, osteolysis, immune suppression, and drug resistance through intercellular communication by transporting specific bioactive cargo, so they can be used as potential biomarkers to assist in diagnosis and new therapeutic strategies for multiple myeloma. This review summarizes the mechanism of MM-EVs remodeling the bone marrow microenvironment to promote the progression of multiple myeloma and their relationship with drug resistance. Finally, we illustrate their research progress as a biomarker and the clinical prospect of promoting the treatment of multiple myeloma including MM-EVs based therapeutic targets for interference communication and engineering modification. The purification and characterization, functional analysis and safety of specific MM-EVs are important challenges for their clinical transformation.
-
Key words:
- extracellular vesicles /
- multiple myeloma /
- bone marrow microenvironment /
- biomarkers
-
-
[1] 冷晴, 刘伟, 管俊. 补体C4在新诊断多发性骨髓瘤患者中的预后价值[J]. 临床血液学杂志, 2023, 36(3): 175-180. doi: 10.13201/j.issn.1004-2806.2023.03.007
[2] van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma[J]. Lancet, 2021, 397(10272): 410-427. doi: 10.1016/S0140-6736(21)00135-5
[3] Marar C, Starich B, Wirtz D. Extracellular vesicles in immunomodulation and tumor progression[J]. Nat Immunol, 2021, 22(5): 560-570. doi: 10.1038/s41590-021-00899-0
[4] Lee JY, Ryu D, Lim SW, et al. Exosomal miR-1305 in the oncogenic activity of hypoxic multiple myeloma cells: a biomarker for predicting prognosis[J]. J Cancer, 2021, 12(10): 2825-2834. doi: 10.7150/jca.55553
[5] Hoelzinger DB, Quinton SJ, Walters DK, et al. Extracellular vesicle proteomic analysis leads to the discovery of HDGF as a new factor in multiple myeloma biology[J]. Blood Adv, 2022, 6(11): 3458-3471. doi: 10.1182/bloodadvances.2021006187
[6] Papanota AM, Karousi P, Kontos CK, et al. Multiple Myeloma Bone Disease: Implication of MicroRNAs in Its Molecular Background[J]. Int J Mol Sci, 2021, 22(5): 2375. doi: 10.3390/ijms22052375
[7] Zhang L, Lei Q, Wang H, et al. Tumor-derived extracellular vesicles inhibit osteogenesis and exacerbate myeloma bone disease[J]. Theranostics, 2019, 9(1): 196-209. doi: 10.7150/thno.27550
[8] Raimondi L, De Luca A, Fontana S, et al. Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis[J]. Cancers, 2020, 12(8): 2167. doi: 10.3390/cancers12082167
[9] Raimondo S, Urzì O, Conigliaro A, et al. Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma[J]. Cancers, 2020, 12(2): 449. doi: 10.3390/cancers12020449
[10] Sun G, Gu Q, Zheng J, et al. Emerging roles of extracellular vesicles in normal and malignant hematopoiesis[J]. J Clin Invest, 2022, 132(18): e160840. doi: 10.1172/JCI160840
[11] Najaflou M, Shahgolzari M, Khosroushahi AY, et al. Tumor-Derived Extracellular Vesicles in Cancer Immunoediting and Their Potential as Oncoimmunotherapeutics[J]. Cancers, 2022, 15(1): 82. doi: 10.3390/cancers15010082
[12] Shao Q, Deng L, Liu H, et al. Involvement of MM cell-derived exosomes in T lymphocytes immune responses[J]. Oncol Lett, 2020, 20(4): 31.
[13] Moloudizargari M, Redegeld F, Asghari MH, et al. Long-chain polyunsaturated omega-3 fatty acids reduce multiple myeloma exosome-mediated suppression of NK cell cytotoxicity[J]. Daru, 2020, 28(2): 647-659. doi: 10.1007/s40199-020-00372-7
[14] Saltarella I, Lamanuzzi A, Apollonio B, et al. Role of Extracellular Vesicle-Based Cell-to-Cell Communication in Multiple Myeloma Progression[J]. Cells, 2021, 10(11): 3185. doi: 10.3390/cells10113185
[15] Laurenzana I, Trino S, Lamorte D, et al. Multiple Myeloma-Derived Extracellular Vesicles Impair Normal Hematopoiesis by Acting on Hematopoietic Stem and Progenitor Cells[J]. Front Med(Lausanne), 2021, 8: 793040.
[16] Bandari SK, Purushothaman A, Ramani VC, et al. Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior[J]. Matrix Biol, 2018, 65: 104-118. doi: 10.1016/j.matbio.2017.09.001
[17] Faict S, Oudaert I, D'Auria L, et al. The Transfer of Sphingomyelinase Contributes to Drug Resistance in Multiple Myeloma[J]. Cancers, 2019, 11(12): 1823. doi: 10.3390/cancers11121823
[18] Tang JX, Chen Q, Li Q, et al. Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib[J]. Cell Biol Int, 2021, 45(5): 965-975. doi: 10.1002/cbin.11540
[19] Yamamoto T, Nakayama J, Yamamoto Y, et al. SORT1/LAMP2-mediated extracellular vesicle secretion and cell adhesion are linked to lenalidomide resistance in multiple myeloma[J]. Blood Adv, 2022, 6(8): 2480-2495. doi: 10.1182/bloodadvances.2021005772
[20] Malavasi F, Faini AC, Morandi F, et al. Molecular dynamics of targeting CD38 in multiple myeloma[J]. Br J Haematol, 2021, 193(3): 581-591. doi: 10.1111/bjh.17329
[21] Brennan K, Iversen KF, Blanco-Fernández A, et al. Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59[J]. Cells, 2022, 11(21): 3365. doi: 10.3390/cells11213365
[22] Lee Y, Ni J, Beretov J, et al. Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis[J]. Mol Cancer, 2023, 22(1): 33. doi: 10.1186/s12943-023-01741-x
[23] Manier S, Liu CJ, Avet-Loiseau H, et al. Prognostic role of circulating exosomal miRNAs in multiple myeloma[J]. Blood, 2017, 129(17): 2429-2436. doi: 10.1182/blood-2016-09-742296
[24] Luo Y, Gui R. Circulating Exosomal CircMYC Is Associated with Recurrence and Bortezomib Resistance in Patients with Multiple Myeloma[J]. Turk J Haematol, 2020, 37(4): 248-262. doi: 10.4274/tjh.galenos.2020.2020.0243
[25] Zhao A, Kong F, Liu CJ, et al. Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition but Apoptosis in Human Proximal Tubular(HK-2) Cells: Implications for Renal Impairment in Multiple Myeloma[J]. Int J Mol Sci, 2017, 18(3): 513. doi: 10.3390/ijms18030513
[26] Sun R, Liu W, Zhao Y, et al. Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage[J]. Cancer Cell Int, 2021, 21(1): 311. doi: 10.1186/s12935-021-02011-w
[27] Lia G, Brunello L, Bruno S, et al. Extracellular vesicles as potential biomarkers of acute graft-vs-host disease[J]. Leukemia, 2018, 32(3): 765-773. doi: 10.1038/leu.2017.277
[28] Laurenzana I, Trino S, Lamorte D, et al. Analysis of Amount, Size, Protein Phenotype and Molecular Content of Circulating Extracellular Vesicles Identifies New Biomarkers in Multiple Myeloma[J]. Int J Nanomedicine, 2021, 16: 3141-3160. doi: 10.2147/IJN.S303391
[29] Cheng Q, Li X, Wang Y, et al. The ceramide pathway is involved in the survival, apoptosis and exosome functions of human multiple myeloma cells in vitro[J]. Acta Pharmacol Sin, 2018, 39(4): 561-568. doi: 10.1038/aps.2017.118
[30] Liu L, Ye Q, Liu L, et al. C6-ceramide treatment inhibits the proangiogenic activity of multiple myeloma exosomes via the miR-29b/Akt pathway[J]. J Transl Med, 2020, 18(1): 298. doi: 10.1186/s12967-020-02468-9
[31] Tu C, Du Z, Zhang H, et al. Endocytic pathway inhibition attenuates extracellular vesicle-induced reduction of chemosensitivity to bortezomib in multiple myeloma cells[J]. Theranostics, 2021, 11(5): 2364-2380. doi: 10.7150/thno.47996
[32] Nishida-Aoki N, Tominaga N, Takeshita F, et al. Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis[J]. Mol Ther, 2017, 25(1): 181-191. doi: 10.1016/j.ymthe.2016.10.009
[33] Zhang X, Zhang H, Gu J, et al. Engineered Extracellular Vesicles for Cancer Therapy[J]. Adv Mater, 2021, 33(14): e2005709. doi: 10.1002/adma.202005709
[34] Vulpis E, Loconte L, Peri A, et al. Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance[J]. J Extracell Vesicles, 2022, 11(1): e12176. doi: 10.1002/jev2.12176
[35] Borrelli C, Ricci B, Vulpis E, et al. Drug-Induced Senescent Multiple Myeloma Cells Elicit NK Cell Proliferation by Direct or Exosome-Mediated IL15 Trans-Presentation[J]. Cancer Immunol Res, 2018, 6(7): 860-869. doi: 10.1158/2326-6066.CIR-17-0604
[36] Wu P, Zhang B, Ocansey DKW, et al. Extracellular vesicles: A bright star of nanomedicine[J]. Biomaterials, 2021, 269: 120467. doi: 10.1016/j.biomaterials.2020.120467
[37] Zhou X, Miao Y, Wang Y, et al. Tumour-derived extracellular vesicle membrane hybrid lipid nanovesicles enhance siRNA delivery by tumour-homing and intracellular freeway transportation[J]. J Extracell Vesicles, 2022, 11(3): e12198. doi: 10.1002/jev2.12198
-
计量
- 文章访问数: 253
- 施引文献: 0
下载: