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DARA acts via complement-dependent and -independent mechanisms. Resistance to DARA may result from upregulation of the complement inhibitory proteins CD55 and CD59, downregulation of the DARA target CD38 on myeloma cells or altered expression of the checkpoint inhibitor ligand programmed death ligand-1 (PD-L1) or other mechanisms. In this study, EVs were isolated from peripheral blood (PB) and bone marrow (BM) from multiple myeloma (MM) patients treated with DARA and PB of healthy controls. EV size and number and the expression of CD38, CD55, CD59 and PD-L1 as well as the EV markers CD9, CD63, CD81, CD147 were determined by flow cytometry. Results reveal that all patient EV samples express CD38, PD-L1, CD55 and CD59. The level of CD55 and CD59 are elevated on MM PB EVs compared with healthy controls, and the level of PD-L1 on MM PB EVs is higher in patients responding to treatment with DARA. CD147, a marker of various aspects of malignant behaviour of cancer cells and a potential target for therapy, was significantly elevated on MM EVs compared with healthy controls. Furthermore, mass spectrometry data suggests that MM PB EVs bind DARA. This study reveals a MM PB and BM EV protein signature that may have diagnostic and prognostic value.<\/jats:p>","DOI":"10.3390\/cells11213365","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T12:29:45Z","timestamp":1666700985000},"page":"3365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59"],"prefix":"10.3390","volume":"11","author":[{"given":"Kieran","family":"Brennan","sequence":"first","affiliation":[{"name":"School of Biomolecular & Biomedical Science, University College Dublin (UCD), Dublin 4, Ireland"},{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4494-9034","authenticated-orcid":false,"given":"Katrine F.","family":"Iversen","sequence":"additional","affiliation":[{"name":"Institute of Regional Health Science, University of Southern Denmark, 7100 Vejle, Denmark"},{"name":"Department of Internal Medicine, Section of Hematology, Lillebaelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Blanco-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core Technology, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Belfield, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Hematology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-6068","authenticated-orcid":false,"given":"Torben","family":"Plesner","sequence":"additional","affiliation":[{"name":"Institute of Regional Health Science, University of Southern Denmark, 7100 Vejle, Denmark"},{"name":"Department of Internal Medicine, Section of Hematology, Lillebaelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-7846","authenticated-orcid":false,"given":"Margaret M.","family":"Mc Gee","sequence":"additional","affiliation":[{"name":"School of Biomolecular & Biomedical Science, University College Dublin (UCD), Dublin 4, Ireland"},{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1182\/blood-2007-10-078022","article-title":"Multiple myeloma","volume":"111","author":"Kyle","year":"2008","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1182\/blood-2012-04-403733","article-title":"Proteasome inhibitors in multiple myeloma: 10 Years later","volume":"120","author":"Moreau","year":"2012","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1002\/ajh.23234","article-title":"Lenalidomide in multiple myeloma: Current status and future potential","volume":"87","author":"Quach","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1506348","article-title":"Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma","volume":"373","author":"Lokhorst","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.4049\/jimmunol.1003032","article-title":"Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors","volume":"186","author":"Tai","year":"2011","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1158\/0008-5472.CAN-18-0773","article-title":"CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma","volume":"79","author":"Marlein","year":"2019","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1486948","DOI":"10.1080\/2162402X.2018.1486948","article-title":"Daratumumab induces CD38 internalization and impairs myeloma cell adhesion","volume":"7","author":"Ghose","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cmet.2017.10.006","article-title":"CD38-NAD+ Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response","volume":"27","author":"Chatterjee","year":"2018","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Martin, T.G., Corzo, K., Chiron, M., Velde, H.V., Abbadessa, G., Campana, F., Solanki, M., Meng, R., Lee, H., and Wiederschain, D. (2019). Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab. Cells, 8.","DOI":"10.3390\/cells8121522"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1182\/blood-2016-03-703439","article-title":"CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma","volume":"128","author":"Nijhof","year":"2016","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/19420862.2015.1007813","article-title":"Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma","volume":"7","author":"Overdijk","year":"2015","journal-title":"MAbs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/bjh.17329","article-title":"Molecular dynamics of targeting CD38 in multiple myeloma","volume":"193","author":"Malavasi","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2040620721989585","DOI":"10.1177\/2040620721989585","article-title":"B-cell maturation antigen (BCMA) in multiple myeloma: The new frontier of targeted therapies","volume":"12","author":"Sanchez","year":"2021","journal-title":"Ther. Adv. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_16","first-page":"3779","article-title":"The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab-containing line of therapy","volume":"138","author":"Szabo","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1038\/leu.2015.123","article-title":"Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab","volume":"29","author":"Nijhof","year":"2015","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1182\/bloodadvances.2021005220","article-title":"Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed\/refractory multiple myeloma","volume":"5","author":"Frerichs","year":"2021","journal-title":"Blood Adv."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Plesner, T., van de Donk, N., and Richardson, P.G. (2020). Controversy in the Use of CD38 Antibody for Treatment of Myeloma: Is High CD38 Expression Good or Bad?. Cells, 9.","DOI":"10.3390\/cells9020378"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by Extracellular Vesicles: Where We Are and Where We Need to Go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.plipres.2017.03.001","article-title":"Lipids in exosomes: Current knowledge and the way forward","volume":"66","author":"Skotland","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nri2567","article-title":"Membrane vesicles as conveyors of immune responses","volume":"9","author":"Thery","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_23","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."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1158\/1078-0432.CCR-10-1489","article-title":"Exosomes and cancer: A newly described pathway of immune suppression","volume":"17","author":"Zhang","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fcell.2018.00018","article-title":"Exosome-Based Cell-Cell Communication in the Tumor Microenvironment","volume":"6","author":"Maia","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_26","first-page":"15","article-title":"Exosomes: Secreted vesicles and intercellular communications","volume":"3","year":"2011","journal-title":"F1000 Biol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/jcp.22773","article-title":"Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy","volume":"227","author":"Ciravolo","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1046\/j.1365-2249.2003.02066.x","article-title":"Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid","volume":"131","author":"Donin","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.it.2004.01.008","article-title":"Complement function in mAb-mediated cancer immunotherapy","volume":"25","author":"Gelderman","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1182\/blood-2016-08-731885","article-title":"Targeting the PD-1\/PD-L1 axis in multiple myeloma: A dream or a reality?","volume":"129","author":"Rosenblatt","year":"2017","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41586-018-0392-8","article-title":"Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response","volume":"560","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nm730","article-title":"Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion","volume":"8","author":"Dong","year":"2002","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1158\/2326-6066.CIR-15-0296","article-title":"Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1","volume":"4","author":"Ishibashi","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/leu.2012.213","article-title":"Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma","volume":"27","author":"Tamura","year":"2013","journal-title":"Leukemia"},{"key":"ref_35","first-page":"8839978","article-title":"Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy","volume":"2021","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Verkleij, C.P.M., Jhatakia, A., Broekmans, M.E.C., Frerichs, K.A., Zweegman, S., Mutis, T., Bezman, N.A., and van de Donk, N. (2020). Preclinical Rationale for Targeting the PD-1\/PD-L1 Axis in Combination with a CD38 Antibody in Multiple Myeloma and Other CD38-Positive Malignancies. Cancers, 12.","DOI":"10.3390\/cancers12123713"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap consortium: Building an international community of software platform partners","volume":"95","author":"Harris","year":"2019","journal-title":"J. Biomed. Inform."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014A metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J. Biomed. Inform."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17319","DOI":"10.1038\/srep17319","article-title":"Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol","volume":"5","author":"Livshits","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/s41598-020-57497-7","article-title":"A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum","volume":"10","author":"Brennan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101112","DOI":"10.1016\/j.tranon.2021.101112","article-title":"Cyclophilin A regulates secretion of tumour-derived extracellular vesicles","volume":"14","author":"Wu","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1021\/acs.jproteome.5b00932","article-title":"Parallel Accumulation-Serial Fragmentation (PASEF): Multiplying Sequencing Speed and Sensitivity by Synchronized Scans in a Trapped Ion Mobility Device","volume":"14","author":"Meier","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1182\/blood-2010-10-299487","article-title":"Consensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1","volume":"117","author":"Rajkumar","year":"2011","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1038\/leu.2012.91","article-title":"Increased expression of extracellular matrix metalloproteinase inducer (CD147) in multiple myeloma: Role in regulation of myeloma cell proliferation","volume":"26","author":"Arendt","year":"2012","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3390\/cimb44010026","article-title":"Soluble CD147 (BSG) as a Prognostic Marker in Multiple Myeloma","volume":"44","author":"Butrym","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/14737159.2019.1583103","article-title":"An update on extracellular vesicles in multiple myeloma: A focus on their role in cell-to-cell cross-talk and as potential liquid biopsy biomarkers","volume":"19","author":"Laurenzana","year":"2019","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15336","DOI":"10.1073\/pnas.1102855108","article-title":"Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3","volume":"108","author":"Aung","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1056\/NEJMra1704286","article-title":"Circulating Extracellular Vesicles in Human Disease","volume":"379","author":"Shah","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cell.2019.02.016","article-title":"Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory","volume":"177","author":"Poggio","year":"2019","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/s41422-018-0060-4","article-title":"Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth","volume":"28","author":"Yang","year":"2018","journal-title":"Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1182\/blood.2021014007","article-title":"Extracellular vesicles and PD-L1 suppress macrophages, inducing therapy resistance in TP53-deficient B-cell malignancies","volume":"139","author":"Izquierdo","year":"2022","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/nm1517","article-title":"Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma","volume":"13","author":"Parsa","year":"2007","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/0008-5472.CAN-14-3362","article-title":"Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer","volume":"76","author":"Lastwika","year":"2016","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1158\/2159-8290.CD-13-0310","article-title":"Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors","volume":"3","author":"Akbay","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1126\/science.aac9935","article-title":"MYC regulates the antitumor immune response through CD47 and PD-L1","volume":"352","author":"Casey","year":"2016","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.aae0477","article-title":"Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity","volume":"353","author":"Dorand","year":"2016","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1084\/jem.20161462","article-title":"What does PD-L1 positive or negative mean?","volume":"213","author":"Ribas","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nature14011","article-title":"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients","volume":"515","author":"Herbst","year":"2014","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1200\/JCO.2015.63.7421","article-title":"Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study","volume":"34","author":"McDermott","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/imr.12389","article-title":"Monoclonal antibodies targeting CD38 in hematological malignancies and beyond","volume":"270","author":"Janmaat","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/cmi.2010.35","article-title":"Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells","volume":"8","author":"You","year":"2011","journal-title":"Cell. Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Xiong, L., Edwards, C.K., and Zhou, L. (2014). The biological function and clinical utilization of CD147 in human diseases: A review of the current scientific literature. Int. J. Mol. Sci., 15.","DOI":"10.3390\/ijms151017411"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1158\/0008-5472.CAN-04-3605","article-title":"Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases","volume":"65","author":"Tang","year":"2005","journal-title":"Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nm.3867","article-title":"The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells","volume":"21","author":"Zhu","year":"2015","journal-title":"Nat. Med."},{"key":"ref_68","first-page":"178","article-title":"Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN","volume":"4","author":"Rahat","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/leu.2015.191","article-title":"Tumor-associated macrophages and extracellular matrix metalloproteinase inducer in prognosis of multiple myeloma","volume":"30","author":"Panchabhai","year":"2016","journal-title":"Leukemia"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/leu.2016.389","article-title":"PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma","volume":"31","author":"Panchabhai","year":"2017","journal-title":"Leukemia"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/21\/3365\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:22Z","timestamp":1760144542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/21\/3365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":70,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["cells11213365"],"URL":"https:\/\/doi.org\/10.3390\/cells11213365","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]}}}