{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:06:03Z","timestamp":1794254763402,"version":"4.9.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"DOI":"10.3389\/fonc.2020.608815","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T08:20:57Z","timestamp":1604564457000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Exosomes in the Pathogenesis and Treatment of Multiple Myeloma in the Context of the Bone Marrow Microenvironment"],"prefix":"10.3389","volume":"10","author":[{"given":"Tianzeng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Moscvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA A Cancer J Clin."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-116129","article-title":"Improved survival in multiple myeloma and the impact of novel therapies","volume":"111","author":"Kumar","year":"2008","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.706287","article-title":"Molecular mechanisms of effectiveness of novel therapies in multiple myeloma","volume":"54","author":"Bianchi","year":"2013","journal-title":"Leuk Lymphoma"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2189","article-title":"Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets","volume":"7","author":"Hideshima","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2013.1.478","article-title":"Monoclonal gammopathy of undetermined significance and smolderingmultiple myeloma: biological insights and early treatment strategies","volume":"2013","author":"Landgren","year":"2013","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000259","article-title":"Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma","volume":"23","author":"Manier","year":"2016","journal-title":"Curr Opin Hematol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-568881","article-title":"Pathogenesis beyond the cancer clone(s) in multiplemyeloma","volume":"125","author":"Bianchi","year":"2015","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/B978-0-12-386469-7.00002-5","article-title":"The Microenvironment and Molecular Biology of the Multiple Myeloma Tumor","volume":"110","author":"Lemaire","year":"2011","journal-title":"Adv Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7792","article-title":"Extracellular vesicle cross-talk in the bone marrow microenvironment: Implications in multiple myeloma","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nri2567","article-title":"Membrane vesicles as conveyors of immune responses","volume":"9","author":"Th\u00e9ry","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Van Niel","year":"2018","journal-title":"Nat Rev Mol Cell Biol [Internet]"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/842849","article-title":"The roles of tumor-derived exosomes in cancerpathogenesis","volume":"2011","author":"Yang","year":"2011","journal-title":"Clin Dev Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/ncrna6030030","article-title":"Emerging insights on the biological impact of extracellularvesicle-associated ncRNAs in multiple Myeloma","volume":"6","author":"Raimondo","year":"2020","journal-title":"Non-coding RNA"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s00018-017-2595-9","article-title":"Current knowledge on exosome biogenesis and release","volume":"75","author":"Hessvik","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"B17","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(18)48095-7","article-title":"Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)","volume":"262","author":"Johnstone","year":"1987","journal-title":"J Biol Chem"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2011.01.002","article-title":"The secreted factors responsible for pre-metastatic niche formation: Old sayings and new thoughts","volume":"21","author":"Peinado","year":"2011","journal-title":"Semin Cancer Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Y\u00e1\u00f1ez-M\u00f3","year":"2015","journal-title":"J Extracell Vesicles"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404296","article-title":"Membrane-derived microvesicles: Important and underappreciated mediators of cell-to-cell communication","volume":"20","author":"Ratajczak","year":"2006","journal-title":"Leukemia"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.91","article-title":"The emerging roles of tumor-derived exosomes in hematological malignancies","volume":"31","author":"Boyiadzis","year":"2017","journal-title":"Leukemia"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.100595","article-title":"The emerging role of exosomes in multiple myeloma","volume":"38","author":"Moloudizargari","year":"2019","journal-title":"Blood Rev"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7150\/jca.31752","article-title":"Potential therapeutic roles of exosomes in multiple myeloma: A systematic review","volume":"10","author":"Li","year":"2019","journal-title":"J Cancer"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66517","article-title":"BM mesenchymal stromal cell \u2013 derived exosomes facilitate multiple myeloma progression Find the latest version: BM mesenchymal stromal cell \u2013 derived exosomes facilitate multiple myeloma progression","volume":"123","author":"Roccaro","year":"2013","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","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":"B26","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2363","article-title":"Exosome-transmitted PSMA3 and PSMA3-AS1 promote proteasome inhibitor resistance in multiple myeloma","volume":"25","author":"Xu","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41375-019-0493-x","article-title":"Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling","volume":"34","author":"Ho","year":"2020","journal-title":"Leukemia"},{"key":"B28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.canlet.2016.04.024","article-title":"Induction of miR-146a by multiple myeloma cells in mesenchymal stromal cells stimulates their pro-tumoral activity","volume":"377","author":"De Veirman","year":"2016","journal-title":"Cancer Lett"},{"key":"B29","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nature01660","article-title":"Control of osteoblast function and regulation of bone mass","volume":"423","author":"Harada","year":"2003","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"33","DOI":"10.4137\/CGM.s16817","article-title":"Bone Disease in Multiple Myeloma: Pathophysiology and Management","volume":"7","author":"Hameed","year":"2014","journal-title":"Cancer Growth Metastasis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/ncrna6030037","article-title":"Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology","volume":"6","author":"Raimondi","year":"2020","journal-title":"Non-Coding RNA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"320","DOI":"10.3390\/cancers12020320","article-title":"The non-coding RNA landscape of plasma celldyscrasias","volume":"12","author":"Morelli","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B36","doi-asserted-by":"publisher","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":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0359-0","article-title":"Exosome-mediated transfer of lncRUNX2-AS1 from multiple myelomacells to MSCs contributes to osteogenesis","volume":"37","author":"Li","year":"2018","journal-title":"Oncogene"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13045-018-0689-y","article-title":"Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG ) and activate the epidermal growth factor pathway in the bone microenvironment leading toosteoclastogenesis","volume":"12","author":"Raimondo","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"449","DOI":"10.3390\/cancers12020449","article-title":"Extracellular Vesicle microRNAs Contribute to the OsteogenicInhibition of Mesenchymal Stem Cells in Multiple Myeloma","volume":"12","author":"Raimondo","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.3390\/cancers12082167","article-title":"Multiple myeloma-derived extracellular vesicles induceosteoclastogenesis through the activation of the XBP1\/IRE1\u03b1 axis","volume":"12","author":"Raimondi","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1136\/jim-2019-001010","article-title":"Multiple myeloma- \u00ad derived exosomes inhibit osteoblastic differentiation and improve IL-6 secretion of BMSCs from multiple myeloma","volume":"68","author":"Liu","year":"2020","journal-title":"J Investig Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41408-018-0139-7","article-title":"Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts","volume":"8","author":"Faict","year":"2018","journal-title":"Blood Cancer J"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079752","article-title":"Upregulation of miR-135b Is Involved in the Impaired Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients","volume":"8","author":"Xu","year":"2013","journal-title":"PLoS ONE"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-576116","article-title":"Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1","volume":"124","author":"Umezu","year":"2014","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-607846","article-title":"Hypoxic exosomes promote angiogenesis Platelets: balancing the septic triad","volume":"124","author":"Fan","year":"2015","journal-title":"Blood"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5046953","article-title":"Structure and Functions of Blood Vessels and Vascular Niches in Bone","volume":"2017","author":"Ramasamy","year":"2017","journal-title":"Stem Cells Int"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000235","article-title":"Exosomes promote bone marrow angiogenesis in hematologic neoplasia: The role of hypoxia","volume":"23","author":"Ohyashiki","year":"2016","journal-title":"Curr Opin Hematol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2016003251","article-title":"Replenishing exosomes from older bone marrow stromal cells withmiR-340 inhibits myeloma-related angiogenesis","volume":"1","author":"Umezu","year":"2017","journal-title":"Blood Adv"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.02.017","article-title":"Angiogenesis in multiple myeloma","volume":"42","author":"Jakob","year":"2006","journal-title":"Eur J Cancer"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2016.1132627","article-title":"The potential diagnostic power of extracellular vesicle analysis for multiple myeloma","volume":"16","author":"Canella","year":"2016","journal-title":"Expert Rev Mol Diagn"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201300142","article-title":"Characterization of Multiple Myeloma Vesicles by Label-Free Relative Quantitation","volume":"13","author":"Harshman","year":"2013","journal-title":"Proteomics"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2554","article-title":"Circulating exosomal long noncoding RNA PRINS\u2014First findings in monoclonal gammopathies","volume":"36","author":"Sedlarikova","year":"2018","journal-title":"Hematol Oncol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.09.005","article-title":"Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis","volume":"26","author":"Melo","year":"2014","journal-title":"Cancer Cell"},{"key":"B54","doi-asserted-by":"publisher","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":"B55","doi-asserted-by":"publisher","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":"B56","doi-asserted-by":"publisher","DOI":"10.14740\/gr925w","article-title":"Autologous Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients With Multiple Myeloma and Hematopoietic Stem Cell Transplantation","volume":"11","author":"Hammami","year":"2018","journal-title":"Gastroenterol Res"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.277","article-title":"Extracellular vesicles as potential biomarkers of acute graft-vs-host disease","volume":"32","author":"Lia","year":"2018","journal-title":"Leukemia"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.118","article-title":"The ceramide pathway is involved in the survival, apoptosis and exosome functions of human multiple myeloma cells in vitro","volume":"39","author":"Cheng","year":"2018","journal-title":"Acta Pharmacol Sin"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.686295","article-title":"Fibronectin on the surface of myeloma cell-derived exosomes mediates exosome-cell interactions","volume":"291","author":"Purushothaman","year":"2016","journal-title":"J Biol Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.182865","article-title":"Phase I study of the heparanase inhibitor International Staging System stage","volume":"103","author":"Galli","year":"2018","journal-title":"Haematologica"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3804","article-title":"Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells","volume":"65","author":"Gastpar","year":"2005","journal-title":"Cancer Res"},{"key":"B62","doi-asserted-by":"publisher","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":"B63","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0604","article-title":"Drug-Induced Senescent Multiple Myeloma Cells Elicit NK CellProliferation by Direct or Exosome-Mediated IL15 Trans-Presentation","volume":"6","author":"Borrelli","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B64","doi-asserted-by":"publisher","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":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.81","article-title":"Getting TRAIL back on track for cancer therapy","volume":"21","author":"Lemke","year":"2014","journal-title":"Cell Death Differ"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2170","article-title":"TNF-related apoptosis-inducing ligand (trail)-armed exosomes deliver proapoptotic signals to tumor site","volume":"22","author":"Rivoltini","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1021\/nn402232g","article-title":"Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors","volume":"7","author":"Jang","year":"2013","journal-title":"ACS Nano"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1038\/s41598-018-20505-y","article-title":"Exosome-Mimetic Nanovesicles from Hepatocytes promote hepatocyte proliferation in vitro and liver regeneration in vivo","volume":"8","author":"Wu","year":"2018","journal-title":"Sci Rep"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.608815\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T14:34:12Z","timestamp":1618238052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.608815\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":68,"alternative-id":["10.3389\/fonc.2020.608815"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.608815","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]},"article-number":"608815"}}