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《Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier》由會員上傳分享，免費在線閱讀，更多相關(guān)內(nèi)容在學術(shù)論文-天天文庫。
1、ARTICLEReceived2Oct2014
2、Accepted20Feb2015
3、Published01Apr2015DOI:10.1038/ncomms7716OPENBrainmetastaticcancercellsreleasemicroRNA-181c-containingextracellularvesiclescapableofdestructingblood–brainbarrierNaoomiTominaga1,2,3,NobuyoshiKosaka1,4,5,MakikoOno1,TakeshiKatsuda1,YusukeYoshioka
4、1,KenjiTamura6,JanLo¨tvall7,HitoshiNakagama2,8&TakahiroOchiya1Brainmetastasisisanimportantcauseofmortalityinbreastcancerpatients.Akeyeventduringbrainmetastasisisthemigrationofcancercellsthroughblood–brainbarrier(BBB).However,themolecularmechanismbehindthepassagethroughthisnaturalbarr
5、ierremainsunclear.Hereweshowthatcancer-derivedextracellularvesicles(EVs),mediatorsofcell–cellcommunicationviadeliveryofproteinsandmicroRNAs(miRNAs),triggerthebreakdownofBBB.Importantly,miR-181cpromotesthedestructionofBBBthroughtheabnormallocalizationofactinviathedownregulationofitsta
6、rgetgene,PDPK1.PDPK1degradationbymiR-181cleadstothedownregulationofphosphorylatedco?linandtheresultantactivatedco?lin-inducedmodulationofactindynamics.Furthermore,wedemonstratethatsystemicinjectionofbrainmetastaticcancercell-derivedEVspromotedbrainmetastasisofbreastcancercelllinesand
7、arepreferentiallyincorporatedintothebraininvivo.Takentogether,theseresultsindicateanovelmechanismofbrainmetastasismediatedbyEVsthattriggersthedestructionofBBB.1DivisionofMolecularandCellularMedicine,NationalCancerCenterResearchInstitute,5-1-1Tsukiji,Chuo-ku,Tokyo104-0045,Japan.2Gradu
8、ateSchoolofMedicine,TheUniversityofTokyo,7-3-1Hongo,Bunkyou-ku,Tokyo113-0033,Japan.3ResearchFellowoftheJapanSocietyforthePromotionofScience(JSPS),Chiyoda-Ku,Tokyo102-0083,Japan.4DepartmentofZoology,UniversityofOxford,TheTinbergenBuilding,SouthParksRoad,OxfordOX13PS,UnitedKingdom.5The
9、JapanSocietyforthePromotionofScience(JSPS)PostdoctoralFellowforResearchAbroad,Chiyoda-Ku,Tokyo102-0083,Japan.6DivisionofBreastandMedicalOncology,NationalCancerCenterResearchInstitute,5-1-1Tsukiji,Chuo-ku,Tokyo104-0045,Japan.7DepartmentofInternalMedicineandDepartmentofRespiratoryMedic
10、ineandAllerg
