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

References

• Bobrie A, Thery C. Exosomes and communication between tumours and the immune system: are all exosomes equal? Biochem Soc Trans 2013; 41:263-7; PMID:23356294; http://dx.doi.org/10.1042/BST20120245
   PubMed Web of Science ®Google Scholar
• Tkach M, Thery C. Communication by extracellular vesicles: Where we are and where we need to go. Cell 2016; 164:1226-32; PMID:26967288; http://dx.doi.org/10.1016/j.cell.2016.01.043
   PubMed Web of Science ®Google Scholar
• Liu Y, Gu Y, Cao X. The exosomes in tumor immunity. Oncoimmunology 2015; 4:e1027472; PMID:26405598; http://dx.doi.org/10.1080/2162402X.2015.1027472
   PubMed Web of Science ®Google Scholar
• Pitt JM, Kroemer G, Zitvogel L. Extracellular vesicles: masters of intercellular communication and potential clinical interventions. J Clin Invest 2016; 126:1139-43; PMID:27035805; http://dx.doi.org/10.1172/JCI87316
   PubMed Web of Science ®Google Scholar
• Lanier LL. NK cell recognition. Ann Rev Immunol 2005; 23:225-74; PMID:15771571; http://dx.doi.org/10.1146/annurev.immunol.23.021704.115526
   PubMed Web of Science ®Google Scholar
• Adib-Conquy M, Scott-Algara D, Cavaillon JM, Souza-Fonseca-Guimaraes F. TLR-mediated activation of NK cells and their role in bacterial/viral immune responses in mammals. Immunol Cell Biol 2014; 92:256-62; PMID:24366517; http://dx.doi.org/10.1038/icb.2013.99
   PubMed Web of Science ®Google Scholar
• Michel T, Poli A, Cuapio A, Briquemont B, Iserentant G, Ollert M, Zimmer J. Human CD56bright NK cells: An update. J Immunol 2016; 196:2923-31; PMID:26994304; http://dx.doi.org/10.4049/jimmunol.1502570
   PubMed Web of Science ®Google Scholar
• Godfrey J, Benson DM, Jr. The role of natural killer cells in immunity against multiple myeloma. Leuk Lymphoma 2012; 53:1666-76; PMID:22423650; http://dx.doi.org/10.3109/10428194.2012.676175
   PubMed Web of Science ®Google Scholar
• Guillerey C, Nakamura K, Vuckovic S, Hill GR, Smyth MJ. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. Cell Mol Life Sci 2016; 73:1569-89; PMID:26801219; http://dx.doi.org/10.1007/s00018-016-2135-z
   PubMed Web of Science ®Google Scholar
• Fionda C, Soriani A, Zingoni A, Santoni A, Cippitelli M. NKG2D and DNAM-1 ligands: molecular targets for NK cell-mediated immunotherapeutic intervention in multiple myeloma. Biomed Res Int 2015; 2015:178698; PMID:26161387; http://dx.doi.org/10.1155/2015/178698
   PubMed Web of Science ®Google Scholar
• Fionda C, Abruzzese MP, Zingoni A, Cecere F, Vulpis E, Peruzzi G, Soriani A, Molfetta R, Paolini R, Ricciardi MR et al. The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma. Oncotarget 2015; 6:23609-30; PMID:26269456; http://dx.doi.org/10.18632/oncotarget.4603
   PubMed Web of Science ®Google Scholar
• Abruzzese MP, Bilotta MT, Fionda C, Zingoni A, Soriani A, Vulpis E, Borrelli C, Zitti B, Petrucci MT, Ricciardi MR et al. Inhibition of bromodomain and extra-terminal (BET) proteins increases NKG2D ligand MICA expression and sensitivity to NK cell-mediated cytotoxicity in multiple myeloma cells: role of cMYC-IRF4-miR-125b interplay. J Hematol Oncol 2016; 9:134; PMID:27903272; http://dx.doi.org/10.1186/s13045-016-0362-2
   PubMed Web of Science ®Google Scholar
• Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, Breckpot K, Brough D, Chaurio R, Cirone M et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol 2015; 6:588; PMID:26635802; http://dx.doi.org/10.3389/fimmu.2015.00588
   PubMed Web of Science ®Google Scholar
• Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 2014; 3:e955691; PMID:25941621; http://dx.doi.org/10.4161/21624011.2014.955691
   PubMed Web of Science ®Google Scholar
• Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature Med 2007; 13:1050-9; PMID:17704786; http://dx.doi.org/10.1038/nm1622
   PubMed Web of Science ®Google Scholar
• Chen T, Guo J, Han C, Yang M, Cao X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J Immunol 2009; 182:1449-59; PMID:19155492; http://dx.doi.org/10.4049/jimmunol.182.3.1449
   PubMed Web of Science ®Google Scholar
• Vacchelli E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch Toll-like receptor agonists for cancer therapy. Oncoimmunology 2013; 2:e22789; PMID:23482847; http://dx.doi.org/10.4161/onci.22789
   PubMed Web of Science ®Google Scholar
• Pradere JP, Dapito DH, Schwabe RF. The Yin and Yang of Toll-like receptors in cancer. Oncogene 2014; 33:3485-95; PMID:23934186; http://dx.doi.org/10.1038/onc.2013.302
   PubMed Web of Science ®Google Scholar
• Soriani A, Zingoni A, Cerboni C, Iannitto ML, Ricciardi MR, Di Gialleonardo V, Cippitelli M, Fionda C, Petrucci MT, Guarini A et al. ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. Blood 2009; 113:3503-11; PMID:19098271; http://dx.doi.org/10.1182/blood-2008-08-173914
   PubMed Web of Science ®Google Scholar
• Antonangeli F, Soriani A, Ricci BM, Ponzetta A, Benigni G, Morrone S, Bernardini G, Santoni A. Natural killer cell recognition of in vivo drug-induced senescent multiple myeloma cells. Oncoimmunology 5:e1218105; PMID:27853638; http://dx.doi.org/10.1080/2162402X.2016.1218105
   PubMed Web of Science ®Google Scholar
• Cerboni C, Fionda C, Soriani A, Zingoni A, Doria M, Cippitelli M, Santoni A. The DNA damage response: a common pathway in the regulation of NKG2D and DNAM-1 ligand expression in normal infected, and cancer cells. Front Immunol 2014; 4:508; PMID:24432022; http://dx.doi.org/10.3389/fimmu.2013.00508
   PubMed Web of Science ®Google Scholar
• Zingoni A, Cecere F, Vulpis E, Fionda C, Molfetta R, Soriani A, Petrucci MT, Ricciardi MR, Fuerst D, Amendola MG et al. Genotoxic stress induces senescence-associated ADAM10-dependent release of NKG2D MIC ligands in multiple myeloma cells. J Immunol 2015; 195:736-48; PMID:26071561; http://dx.doi.org/10.4049/jimmunol.1402643
   PubMed Web of Science ®Google Scholar
• Reiners KS, Dassler J, Coch C, Pogge von Strandmann E. Role of exosomes released by dendritic cells and/or by tumor targets: regulation of NK cell plasticity. Front Immunol 2014; 5:91; PMID:24639679; http://dx.doi.org/10.3389/fimmu.2014.00091
   PubMed Web of Science ®Google Scholar
• Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol 2008; 180:7249-58; PMID:18490724; http://dx.doi.org/10.4049/jimmunol.180.11.7249
   PubMed Web of Science ®Google Scholar
• Ashiru O, Boutet P, Fernandez-Messina L, Aguera-Gonzalez S, Skepper JN, Vales-Gomez M, Reyburn HT. Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes. Cancer Res 2010; 70:481-9; PMID:20068167; http://dx.doi.org/10.1158/0008-5472.CAN-09-1688
   PubMed Web of Science ®Google Scholar
• Berchem G, Noman MZ, Bosseler M, Paggetti J, Baconnais S, Le Cam E, Nanbakhsh A, Moussay E, Mami-Chouaib F, Janji B et al. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-beta and miR23a transfer. Oncoimmunology 2016; 5:e1062968; PMID:27141372; http://dx.doi.org/10.1080/2162402X.2015.1062968
   PubMed Web of Science ®Google Scholar
• Labani-Motlagh A, Israelsson P, Ottander U, Lundin E, Nagaev I, Nagaeva O, Dehlin E, Baranov V, Mincheva-Nilsson L. Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumour Biol 2016; 37:5455-66; PMID:26563374; http://dx.doi.org/10.1007/s13277-015-4313-2
   PubMed Web of Science ®Google Scholar
• Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y, Kappes JC, Barnes S, Kimberly RP, Grizzle WE et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol 2006; 176:1375; PMID:16424164; http://dx.doi.org/10.4049/jimmunol.176.3.1375
   PubMed Web of Science ®Google Scholar
• Szcepanski MJ, Szajinik M, Welsh A, Whiteside TL, Boyiadzis M. Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor beta1. Haematologica 2011; 96:1302-09; PMID:21606166; http://dx.doi.org/10.3324/haematol.2010.0397433
   PubMed Web of Science ®Google Scholar
• Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res 2007; 67:7458-66; PMID:17671216; http://dx.doi.org/10.1158/0008-5472.CAN-06-3456
   PubMed Web of Science ®Google Scholar
• Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 2005; 65:5238-47; PMID:15958569; http://dx.doi.org/10.1158/0008-5472.CAN-04-3804
   PubMed Web of Science ®Google Scholar
• Lv LH, Wan YL, Lin Y, Zhang W, Yang M, Li GL, Lin HM, Shang CZ, Chen YJ, Min J. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro. J Biol Chem 2012; 287:15874-85; PMID:22396543; http://dx.doi.org/10.1074/jbc.M112.340588
   PubMed Web of Science ®Google Scholar
• Reiners KS, Topolar D, Henke A, Simhadri VR, Kessler J, Sauer M, Bessler M, Hansen HP, Tawadros S, Herling M et al. Soluble ligands for NK cell receptors promote evasion from chronic lymphocytic leukemia cells from NK cell anti-tumor activity. Blood 2013; 121:3658-65; PMID:23509156; http://dx.doi.org/10.1182/blood-2013-01-476606
   PubMed Web of Science ®Google Scholar
• Daβler-Plenker J, Reiners KS, van den Boorn JG, Hansen HP, Putschli B, Barnert S, Schuberth-Wagner C, Schubert R, Tüting T, Hallek M et al. RIG-I activation induces the release of extracellular vesicles with antitumor activity. Oncoimmunology 2016; 19:e1218827; PMID:27853642; http://dx.doi.org/10.1080/2162402X.2016.1219827
   Web of Science ®Google Scholar
• Thery C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Prot Cell Biol 2006; Chapter 3:Unit 3.22; PMID:18228490; http://dx.doi.org/10.1002/0471143030.cb0322s30
   PubMedGoogle Scholar
• Nabi IR, Le PU. Caveolae/raft-dependent endocytosis. J Cell Biol 2003; 161:673-77; PMID:12771123; http://dx.doi.org/10.1083/jcb.200302028
   PubMed Web of Science ®Google Scholar
• Sica A, Dorman L, Viggiano V, Cippitelli M, Ghosh P, Rice N, Young HA. Interaction of NF-kappaB and NFAT with the interferon-gamma promoter. J Biol Chem 1997; 272:30412-20; PMID:9374532; http://dx.doi.org/10.1074/jbc.272.48.30412
   PubMed Web of Science ®Google Scholar
• Chow A, Zhou W, Liu L, Fong MY, Champer J, Van Haute D, Chin AR, Ren X, Gugiu BG, Meng Z et al. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-kappaB. Sci Rep 2014; 4:5750; PMID:25034888; http://dx.doi.org/10.1038/srep05750
   PubMed Web of Science ®Google Scholar
• Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, Boireau W, Rouleau A, Simon B, Lanneau D et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 2010; 120:457-71 PMID:20093776; http://dx.doi.org/10.1172/JCI40483
   PubMed Web of Science ®Google Scholar
• Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA 2012; 109:E2110-6; PMID:22753494; http://dx.doi.org/10.1073/pnas.1209414109
   PubMed Web of Science ®Google Scholar
• He S, Chu J, Wu LC, Mao H, Peng Y, Alvarez-Breckenridge CA, Hughes T, Wei M, Zhang J, Yuan S et al. MicroRNAs activate natural killer cells through Toll-like receptor signaling. Blood 2013; 121:4663-71; PMID:23580661; http://dx.doi.org/10.1182/blood-2012-07-441360
   PubMed Web of Science ®Google Scholar
• Stangl S, Gehrmann M, Riegger J, Kuhs K, Riederer I, Sievert W, Hube K, Mocikat R, Dressel R, Kremmer E et al. Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc Natl Acad Sci U S A 2011; 108:733-8; PMID:21187371; http://dx.doi.org/10.1073/pnas.1016065108
   PubMed Web of Science ®Google Scholar
• Gobbo J, Marcion G, Cordonnier M, Dias AM, Pernet N, Hammann A, Richaud S, Mjahed H, Isambert N, Clausse V et al. Restoring anticancer immune response by targeting tumor-derived exosomes with a HSP70 peptide aptamer. J Natl Cancer Inst 2016; 108:djv330; PMID:26598503; http://dx.doi.org/10.1093/jnci/djv330
   PubMedGoogle Scholar
• Gunther S, Ostheimer C, Stangl S, Specht HM, Mozes P, Jesinghaus M, Vordermark D, Combs SE, Peltz F, Jung MP et al. Correlation of Hsp70 serum levels with gross tumor volume and composition of lymphocyte subpopulations in patients with squamous cell and adeno non-small cell lung cancer. Front Immunol 2015; 6:556; PMID:26579130; http://dx.doi.org/10.3389/fimmu.2015.00556
   PubMed Web of Science ®Google Scholar
• Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 2005; 10:86-103; PMID:16038406; http://dx.doi.org/10.1379/CSC-99r.110.1379/CSC-99r.1
   PubMed Web of Science ®Google Scholar
• Pitt JM, Andre F, Amigorena S, Soria JC, Eggermont A, Kroemer G, Zitvogel L. Dendritic cell-derived exosomes for cancer therapy. J Clin Invest 2016; 126:1224-32; PMID:27035813; http://dx.doi.org/10.1172/JCI81137
   PubMed Web of Science ®Google Scholar
• Zhang X, Pei Z, Chei J, Ji C, Xu J, Zhang X, Wang J. Exosomes for immunoregulation and therapeutic interventention in cancer. J Cancer 2016; 7:1081-7; PMID:27326251; http://dx.doi.org/10.7150/jca.14866
   PubMed Web of Science ®Google Scholar
• Umezu T, Tadokoro H, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki JH. Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. Blood 2014; 124:3748-57; PMID:25320245; http://dx.doi.org/10.1182/blood-2014-05-576116
   PubMed Web of Science ®Google Scholar
• Purushothaman A, Bandari SK, Liu J, Mobley JA, Brown EE, Sanderson RD. Fibronectin on the Surface of Myeloma Cell-derived Exosomes Mediates Exosome-Cell Interactions. J Biol Chem 2016; 291:1652-63; PMID:26601950; http://dx.doi.org/10.1074/jbc.M115.686295
   PubMed Web of Science ®Google Scholar
• Lu H, Yang Y, Gad E, Inatsuka C, Wenner CA, Disis ML, Standish LJ. TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapy. Clin Cancer Res 2011; 17:6742-53; PMID:21918170; http://dx.doi.org/10.1158/1078-0432.CCR-11-1142
   PubMed Web of Science ®Google Scholar
• Deng Y, Chu J, Ren Y, Fan Z, Ji X, Mundy-Bosse B, Yuan S, Hughes T, Zhang J, Cheema B et al. The natural product phyllanthusmin C enhances IFN-gamma production by human NK cells through upregulation of TLR-mediated NF-kappaB signaling. J Immunol 2014; 193:2994-3002; PMID:25122922; http://dx.doi.org/10.4049/jimmunol.1302600
   PubMed Web of Science ®Google Scholar
• Batoni G, Esin S, Favilli F, Pardini M, Bottai D, Maisetta G, Florio W, Campa M. Human CD56bright and CD56dim natural killer cell subsets respond differentially to direct stimulation with Mycobacterium bovis bacillus Calmette-Guerin. Scand J Immunol 2005; 62:498-506; PMID:16316416; http://dx.doi.org/10.1111/j.1365-3083.2005.01692.x
   PubMed Web of Science ®Google Scholar
• Girart MV, Fuertes MB, Domaica CI, Rossi LE, Zwirner NW. Engagement of TLR3, TLR7, and NKG2D regulate IFN-gamma secretion but not NKG2D-mediated cytotoxicity by human NK cells stimulated with suboptimal doses of IL-12. J Immunol 2007; 179:3472-9; PMID:17804388; http://dx.doi.org/10.4049/jimmunol.179.6.3472
   PubMed Web of Science ®Google Scholar
• Millard AL, Spirig R, Mueller NJ, Seebach JD, Rieben R. Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate. Mol Immunol 2010; 47:2349-58; PMID:20541808; http://dx.doi.org/10.1016/j.molimm.2010.05.284
   PubMed Web of Science ®Google Scholar
• Esin S, Counoupas C, Aulicino A, Brancatisano FL, Maisetta G, Bottai D, Di Luca M, Florio W, Campa M, Batoni G. Interaction of Mycobacterium tuberculosis cell wall components with the human natural killer cell receptors NKp44 and Toll-like receptor 2. Scand J Immunol 2013; 77:460-9; PMID:23578092; http://dx.doi.org/10.1111/sji.12052
   PubMed Web of Science ®Google Scholar
• Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 2002; 277:15028-34; PMID:11836257; http://dx.doi.org/10.1074/jbc.M200497200
   PubMed Web of Science ®Google Scholar
• Mathur S, Walley KR, Wang Y, Indrambarya T, Boyd JH. Extracellular heat shock protein 70 induces cardiomyocyte inflammation and contractile dysfunction via TLR2. Circ J 2011; 75:2445-52; PMID:21817814; http://dx.doi.org/10.1253/circj.CJ-11-0194
   PubMed Web of Science ®Google Scholar
• Multhoff G. Heat shock protein 70 (Hsp70): membrane location, export and immunological relevance. Methods 2007; 43:229-37; PMID:17920520; http://dx.doi.org/10.1016/j.ymeth.2007.06.006
   PubMed Web of Science ®Google Scholar
• Lancaster GI, Febbraio MA. Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem 2005; 280:23349-55;PMID:15826944; http://dx.doi.org/10.1074/jbc.M502017200
   PubMed Web of Science ®Google Scholar
• Xie Y, Bai O, Zhang H, Yuan J, Zong S, Chibbar R, Slattery K, Qureshi M, Wei Y, Deng Y et al. 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. J Cell Mol Med 2010; 14:2655-66; PMID:19627400; http://dx.doi.org/10.1111/j.1582-4934.2009.00851.x
   PubMed Web of Science ®Google Scholar
• Seya T, Shime H, Takeda Y, Tatematsu M, Takashima K, Matsumoto M. Adjuvant for vaccine immunotherapy of cancer–focusing on Toll-like receptor 2 and 3 agonists for safely enhancing antitumor immunity. Cancer Sci 2015; 106:1659-68; PMID:26395101; http://dx.doi.org/10.1111/cas.12824
   PubMed Web of Science ®Google Scholar
• Rerole AL, Gobbo J, De Thonel A, Schmitt E, Pais de Barros JP, Hammann A, Lanneau D, Fourmaux E, Demidov ON, Micheau O et al. Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res 2011; 71:484-95; PMID:21224349; http://dx.doi.org/10.1158/0008-5472.CAN-10-1443
   PubMed Web of Science ®Google Scholar
• Provencher SW. CONTIN: a general purpose constrained regularization program for inverting noisy linear algebraic and integral equations. Computer Physics Communications 1982; 27:229-42; http://dx.doi.org/10.1016/0010-4655(82)90174-6
   Web of Science ®Google Scholar
• Palmieri V, Lucchetti D, Gatto I, Maiorana A, Marcantoni M, Maulucci G, Papi M, Pola R, De Spirito M, Sgambato A. Dynamic light scattering for the characterization and counting of extracellular vesicles: a powerful noninvasive tool. J Nanopart Res 2014; 16:1-8; http://dx.doi.org/10.1007/s11051-014-2583-z
   Web of Science ®Google Scholar
• Papi M, Arcovito G, De Spirito M, Amiconi G, Bellelli A, Boumis G. Simultaneous static and dynamic light scattering approach to the characterization of the different fibrin gel structures occurring by changing chloride concentration. Appl Phys Lett 2005; 86:18391; http://dx.doi.org/10.1063/1.1915526
   Web of Science ®Google Scholar
• Bernardini G, Kim JY, Gismondi A, Butcher EC, Santoni A. Chemoatractant induces LFA-1 associated PI 3K activity and cell migration that are dependent on Fyn signaling. FASEB J 2005; 19:1305-7; PMID:15955842; http://dx.doi.org/10.1096/fj.04-3352fje
   PubMed Web of Science ®Google Scholar
• Fionda C, Nappi F, Piccoli M, Frati L, Santoni A, Cippitelli M. 15-deoxy-Delta12,14-prostaglandin J2 negatively regulates rankl gene expression in activated T lymphocytes: role of NF-kappaB and early growth response transcription factors. J Immunol 2007; 178:4039-50;PMID:17371958;http://dx.doi.org/10.4049/jimmunol.178.7.4039
   PubMed Web of Science ®Google Scholar
• Zingoni A, Palmieri G, Morrone S, Carretero M, Lopez-Botet M, Santoni A. CD69-triggered ERK activation and functions are negatively regulated by CD94/NKG2A inhibitory receptor. Eur J Immunol 2000; 30:644-51; PMID:10671222; http://dx.doi.org/10.1002/1521-4141(200002)30:2%3c644::AID-IMMU644%3e3.0.CO;2-H
   PubMed Web of Science ®Google Scholar
• Gasparrini F, Molfetta R, Quatrini L, Frati L, Santoni A, Paolini R. Syk-dependent regulation of Hrs phosphorylation and ubiquitination upon FcϵRI engagement: impact on Hrs membrane/cytosol localization. Eur J Immunol 2012; 42:2744-53; PMID:22706924; http://dx.doi.org/10.1002/eji.201142278
   PubMed Web of Science ®Google Scholar