000070347 001__ 70347
000070347 005__ 20200324135212.0
000070347 0247_ $$2doi$$a10.1016/j.canlet.2016.10.005
000070347 0248_ $$2sideral$$a96634
000070347 037__ $$aART-2016-96634
000070347 041__ $$aeng
000070347 100__ $$0(orcid)0000-0002-8486-8514$$aMiguel, D. de
000070347 245__ $$aHigh-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer
000070347 260__ $$c2016
000070347 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070347 5203_ $$aDuring the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials. In this study we have tested LUV-TRAIL in several human colon cancer cell lines with different sensitivity to sTRAIL. LUV-TRAIL significantly improved sTRAIL cytotoxicity in all colon cancer cell lines tested. Trying to ascertain the molecular mechanism by which LUV-TRAIL exhibited improved cytotoxicity, we demonstrated that TRAIL-coated lipid nanoparticles were able to activate DR5 more efficiently than sTRAIL, and this relied on LUV-TRAIL ability to promote DR5 clustering on the cell surface. Moreover, we show that TRAIL molecules are arranged in higher order oligomers only in LUV-TRAIL, which may explain their enhanced DR5 clustering ability. Finally, LUV-TRAIL showed significantly better antitumour activity than sTRAIL in an in vivo model using HCT-116 xenograft tumours in nude mice, validating its potential clinical application.
000070347 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI13-00416$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2013-48626-C2-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2011-28262-C04-01
000070347 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000070347 590__ $$a6.375$$b2016
000070347 591__ $$aONCOLOGY$$b25 / 217 = 0.115$$c2016$$dQ1$$eT1
000070347 592__ $$a2.371$$b2016
000070347 593__ $$aOncology$$c2016$$dQ1
000070347 593__ $$aCancer Research$$c2016$$dQ1
000070347 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000070347 700__ $$aGallego-Lleyda, A.
000070347 700__ $$0(orcid)0000-0002-9414-1845$$aAyuso, J. M.$$uUniversidad de Zaragoza
000070347 700__ $$aPejenaute-Ochoa, D.
000070347 700__ $$0(orcid)0000-0002-7886-7013$$aJarauta, V.
000070347 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, I.$$uUniversidad de Zaragoza
000070347 700__ $$0(orcid)0000-0001-5376-4440$$aFernández, L. J.$$uUniversidad de Zaragoza
000070347 700__ $$aOchoa, I.
000070347 700__ $$0(orcid)0000-0003-4115-9766$$aConde, B.$$uUniversidad de Zaragoza
000070347 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza
000070347 700__ $$0(orcid)0000-0003-3043-147X$$aMartinez-Lostao, L.$$uUniversidad de Zaragoza
000070347 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000070347 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000070347 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000070347 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000070347 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000070347 773__ $$g383, 2 (2016), 250-260$$pCancer lett.$$tCANCER LETTERS$$x0304-3835
000070347 8564_ $$s693890$$uhttps://zaguan.unizar.es/record/70347/files/texto_completo.pdf$$yPostprint
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000070347 909CO $$ooai:zaguan.unizar.es:70347$$particulos$$pdriver
000070347 951__ $$a2020-03-24-10:00:53
000070347 980__ $$aARTICLE