{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:29:57Z","timestamp":1789543797661,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs) were shown to modulate the expression of genes critical for MM pathogenesis. In addition, miRNAs are secreted via extracellular vesicles (EVs), which are released from various cell types including MM cells, and these miRNAs are involved in multiple types of cell-cell interactions, which lead to the malignancy of MM. In this review, we summarize the current knowledge regarding the role of miRNA secretion via EVs and of EVs themselves in MM development. We also discuss the potential clinical applications of EVs as promising biomarkers and new therapeutic targets for improving the outcome of MM, resulting in a brighter future for aging societies.<\/jats:p>","DOI":"10.3390\/jcm7030055","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T13:13:48Z","timestamp":1520860428000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma"],"prefix":"10.3390","volume":"7","author":[{"given":"Tomofumi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"},{"name":"Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyoshi","family":"Kosaka","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Hattori","sequence":"additional","affiliation":[{"name":"Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ochiya","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1242\/jcs.113.19.3365","article-title":"Exosome: From internal vesicle of the multivesicular body to intercellular signaling device","volume":"19","author":"Denzer","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tcb.2015.01.004","article-title":"Ectosomes and exosomes: Shedding the confusion between extracellular vesicles","volume":"25","author":"Cocucci","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20424","DOI":"10.3402\/jev.v2i0.20424","article-title":"Comparative marker analysis of extracellular vesicles in different human cancer types","volume":"2","author":"Yoshioka","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1586\/epr.09.17","article-title":"Exosomes: Proteomic insights and diagnostic potential","volume":"6","author":"Simpson","year":"2009","journal-title":"Expert Rev. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tcb.2008.11.003","article-title":"Shedding microvesicles: Artefacts no more","volume":"19","author":"Cocucci","year":"2009","journal-title":"Trends Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3389\/fgene.2013.00173","article-title":"Trash or Treasure: Extracellular microRNAs and cell-to-cell communication","volume":"4","author":"Kosaka","year":"2013","journal-title":"Front. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Boil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6328","DOI":"10.1073\/pnas.0914843107","article-title":"Functional delivery of viral miRNAs via exosomes","volume":"107","author":"Pegtel","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1074\/jbc.M111.288662","article-title":"Competitive interactions of cancer cells and normal cells via secretory microRNAs","volume":"287","author":"Kosaka","year":"2012","journal-title":"J. Boil. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.molcel.2010.06.010","article-title":"Secreted monocytic miR-150 enhances targeted endothelial cell migration","volume":"39","author":"Zhang","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17442","DOI":"10.1074\/jbc.M110.107821","article-title":"Secretory mechanisms and intercellular transfer of microRNAs in living cells","volume":"285","author":"Kosaka","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nrc.2017.69","article-title":"Classifying the evolutionary and ecological features of neoplasms","volume":"17","author":"Maley","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1038\/onc.2014.300","article-title":"Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes","volume":"34","author":"Cui","year":"2015","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10555-007-9066-y","article-title":"Hypoxia: A key regulator of angiogenesis in cancer","volume":"26","author":"Liao","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1172\/JCI70212","article-title":"Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer","volume":"123","author":"Welti","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1038\/emboj.2012.183","article-title":"Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway","volume":"31","author":"Zhuang","year":"2012","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10849","DOI":"10.1074\/jbc.M112.446831","article-title":"Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis","volume":"288","author":"Kosaka","year":"2013","journal-title":"J. Boil. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1038\/onc.2017.105","article-title":"Hypoxic lung cancer secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1","volume":"36","author":"Hsu","year":"2017","journal-title":"Oncogene"},{"key":"ref_21","first-page":"E3234","article-title":"Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis","volume":"111","author":"Wang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1549-8719.2011.00154.x","article-title":"miR-210: The master hypoxamir","volume":"19","author":"Chan","year":"2012","journal-title":"Microcirculation"},{"key":"ref_23","first-page":"920509","article-title":"Blood-brain barrier integrity and breast cancer metastasis to the brain","volume":"2011","author":"Arshad","year":"2010","journal-title":"Pathol. Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Aguado, B.A., Bushnell, G.G., Rao, S.S., Jeruss, J.S., and Shea, L.D. (2017). Engineering the pre-metastatic niche. Nat. Biomed. Eng., 1.","DOI":"10.1038\/s41551-017-0077"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/ncb3169","article-title":"Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver","volume":"17","author":"Aiello","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6716","DOI":"10.1038\/ncomms7716","article-title":"Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier","volume":"6","author":"Tominaga","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.1158\/0008-5472.CAN-11-0241","article-title":"Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche","volume":"71","author":"Grange","year":"2011","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/path.4712","article-title":"Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression","volume":"239","author":"Wang","year":"2016","journal-title":"J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1158\/1078-0432.CCR-10-2476","article-title":"SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase\/syndecan-1 axis","volume":"17","author":"Ritchie","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9012152","DOI":"10.1155\/2017\/9012152","article-title":"Multiple myeloma-derived exosomes regulate the functions of mesenchymal stem cells partially via modulating miR-21 and miR-146a","volume":"2017","author":"Cheng","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1158\/1538-7445.NONRNA15-A17","article-title":"Induction of miR-146a by multiple myeloma cells in mesenchymal stromal cells stimulates their pro-tumoral activity","volume":"377","author":"Wang","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nri855","article-title":"Exosomes: Composition, biogenesis and function","volume":"2","author":"Zitvogel","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1083\/jcb.147.3.599","article-title":"Molecular characterization of dendriticcell-derived exosomes. Selective accumulation of the heat-shock protein hsc73","volume":"147","author":"Regnault","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nm0598-594","article-title":"Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes","volume":"4","author":"Zitvogel","year":"1998","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/85438","article-title":"Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming","volume":"7","author":"Wolfers","year":"2001","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nrc3581","article-title":"History of myeloid-derived suppressor cells","volume":"13","author":"Talmadge","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_38","first-page":"457","article-title":"Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells","volume":"120","author":"Chalmin","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14684","DOI":"10.1038\/s41598-017-14661-w","article-title":"Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemia","volume":"7","author":"Hong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1368823","DOI":"10.1080\/20013078.2017.1368823","article-title":"Dominant immunosuppression of dendritic cell function by prostate-cancer-derived exosomes","volume":"6","author":"Salimu","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/s41467-017-01433-3","article-title":"Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche","volume":"8","author":"Plebanek","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1158\/1078-0432.CCR-17-2664","article-title":"Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients","volume":"24","author":"Theodoraki","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/bjc.2017.389","article-title":"Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response","volume":"118","author":"Yang","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Guo, D., Chen, Y., Wang, S., Yu, L., Shen, Y., Zhong, H., and Yang, Y. (2017). Exosomes from heat-stressed tumour cells inhibit tumour growth by converting regulatory T cells to Th17 cells via IL-6. Immunology.","DOI":"10.1111\/imm.12874"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, Q., Huang, Q., Huyan, T., Wang, Y., Huang, Q., and Shi, J. (2017). Bifacial effects of engineering tumour cell-derived exosomes on human natural killer cells. Exp. Cell Res.","DOI":"10.1016\/j.yexcr.2017.12.005"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1111\/j.1582-4934.2009.00851.x","article-title":"Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8(+) CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70","volume":"14","author":"Xie","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/CJI.0000000000000185","article-title":"DCOne as an allogeneic cell-based vaccine for multiple myeloma","volume":"40","author":"Leaf","year":"2017","journal-title":"J. Immunother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43992","DOI":"10.18632\/oncotarget.6083","article-title":"The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_49","first-page":"21","article-title":"Tumor necrosis factor gene-engineered J558 tumor cell-released exosomes stimulate tumor antigen P1A-specific CD8+ CTL responses and antitumor immunity","volume":"25","author":"Xie","year":"2010","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.molonc.2014.01.012","article-title":"miRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization","volume":"8","author":"Valencia","year":"2014","journal-title":"Mol. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1038\/s41598-017-03460-y","article-title":"Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway","volume":"7","author":"Taverna","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16015","DOI":"10.1038\/celldisc.2016.15","article-title":"Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity","volume":"2","author":"Sun","year":"2016","journal-title":"Cell Discov."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hashimoto, K., Ochi, H., Sunamura, S., Kosaka, N., Mabuchi, Y., Fukuda, T., Yao, K., Kanda, H., Ae, K., and Okawa, A. (2018). Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A. Proc. Natl. Acad. Sci. USA.","DOI":"10.1073\/pnas.1717363115"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13772","DOI":"10.18632\/oncotarget.3830","article-title":"Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation","volume":"6","author":"Raimondi","year":"2015","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27343","DOI":"10.18632\/oncotarget.4398","article-title":"Inhibition of miR-21 restores RANKL\/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts","volume":"6","author":"Pitari","year":"2015","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.yexcr.2017.12.001","article-title":"Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365","volume":"362","author":"Min","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5369","DOI":"10.1038\/onc.2017.134","article-title":"Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma","volume":"36","author":"Zeng","year":"2017","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e1362530","DOI":"10.1080\/2162402X.2017.1362530","article-title":"Resistance to HER2-targeted anti-cancer drugs is associated with immune evasion in cancer cells and their derived extracellular vesicles","volume":"6","author":"Martinez","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1159\/000485780","article-title":"Exosomal microRNA miR-1246 promotes cell proliferation, invasion and drug resistance by targeting CCNG2 in breast cancer","volume":"44","author":"Li","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Samuel, P., Mulcahy, L.A., Furlong, F., McCarthy, H.O., Brooks, S.A., Fabbri, M., Pink, R.C., and Carter, D.R.F. (2018). Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells. Philos. Trans. R. Soc. Lond. B Biol. Sci., 373.","DOI":"10.1098\/rstb.2017.0065"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.2147\/IJN.S131516","article-title":"Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner","volume":"12","author":"Qin","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"60698","DOI":"10.18632\/oncotarget.10849","article-title":"Microenvironment drug resistance in multiple myeloma: Emerging new players","volume":"7","author":"Desantis","year":"2016","journal-title":"Oncotarget"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1182\/blood-2014-03-562439","article-title":"Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells","volume":"124","author":"Wang","year":"2014","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e1279372","DOI":"10.1080\/2162402X.2017.1279372","article-title":"Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70\/TLR2\/NF-kB axis","volume":"6","author":"Vulpis","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1756-8722-4-37","article-title":"Suppressing miRNA-15a\/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells","volume":"4","author":"Hao","year":"2011","journal-title":"J. Hematol. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/leu.2014.279","article-title":"MiR-29b replacement inhibits proteasomes and disrupts aggresome+autophagosome formation to enhance the antimyeloma benefit of bortezomib","volume":"29","author":"Jagannathan","year":"2015","journal-title":"Leukemia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1182\/blood-2016-09-742296","article-title":"Prognostic role of circulating exosomal miRNAs in multiple myeloma","volume":"129","author":"Manier","year":"2017","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e456","DOI":"10.3324\/haematol.2017.168070","article-title":"Circulating microRNA expressions can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory\/relapsed multiple myeloma","volume":"102","author":"Jung","year":"2017","journal-title":"Haematologica"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"30876","DOI":"10.18632\/oncotarget.9021","article-title":"Potential role of exosome-associated microRNA panels and in vivo environment to predict drug resistance for patients with multiple myeloma","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1056\/NEJMoa1607751","article-title":"Daratumumab, lenalidomide, and dexamethasone for multiple myeloma","volume":"375","author":"Dimopoulos","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9739","DOI":"10.1007\/s13277-015-3741-3","article-title":"High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders","volume":"36","author":"Caivano","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/nyas.12485","article-title":"Unraveling the contribution of ectoenzymes to myeloma life and survival in the bone marrow niche","volume":"1335","author":"Quarona","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.micron.2013.08.010","article-title":"Plasma cells release membrane microparticles in a mouse model of multiple myeloma","volume":"54\u201355","author":"Benameur","year":"2013","journal-title":"Micron"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ymthe.2016.10.009","article-title":"Disruption of circulating extracellular vesicles as a novel therapeutic strategy against cancer metastasis","volume":"25","author":"Tominaga","year":"2017","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/mt.2012.180","article-title":"Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells","volume":"21","author":"Ohno","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/mt.2010.105","article-title":"A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes","volume":"18","author":"Sun","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2015.03.033","article-title":"Exosomes as drug delivery vehicles for Parkinson\u2019s disease therapy","volume":"207","author":"Haney","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1186\/1478-811X-11-88","article-title":"Exosomes are natural carriers of exogenous siRNA to human cells in vitro","volume":"11","author":"Shtam","year":"2013","journal-title":"Cell Commun. Signal."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1056\/NEJMoa01133202","article-title":"A long-term study of prognosis of monoclonal gammopathy of undetermined significance","volume":"346","author":"Kyle","year":"2002","journal-title":"N. Engl. J. 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