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Antiangiogenic and Antitumor Effects of Trypanosoma cruzi Calreticulin 英文参考文献
AntiangiogenicandAntitumorEffectsofTrypanosoma
cruziCalreticulin
NandyC.Lo′pez1,CarolinaValck1,GaliaRam?′rez1,MargaritaRodr?′guez1,CarolinaRibeiro1 ,Juana
Orellana1,IsmaelMaldonado1,AdrianaAlbini2,DanielAnacona1,DavidLemus1,LorenaAguilar1,
WilhelmSchwaeble3,ArturoFerreira1*
1InstituteofBiomedicalSciences,FacultyofMedicine,UniversityofChile,Santiago,Chile,2OncologyResearch,ScienceandTechnologyPole,IRCCSMultimedica,Milan,
Italy,3DepartmentofInfection,ImmunityandInflammation,UniversityofLeicester,Leicester,UnitedKingdom
Abstract
Background:InLatinAmerica,18millionpeopleareinfectedwithTrypanosomacruzi,theagentofChagas’disease,withthe
greatest economic burden. Vertebrate calreticulins (CRT) are multifunctional, intra- and extracellular proteins. In the
endoplasmic reticulum (ER) they bind calcium and act as chaperones. Since human CRT (HuCRT) is antiangiogenic and
suppressestumorgrowth,thepresenceofthesefunctionsintheparasiteorthologuemayhaveconsequencesinthehost/
parasite interaction. Previously, we have cloned and expressed T. cruzi calreticulin (TcCRT) and shown that TcCRT,
translocated from the ER to the area of trypomastigote flagellum emergence, promotes infectivity, inactivates the
complement system and inhibits angiogenesis in the chorioallantoid chicken egg membrane. Most likely, derived from
theseproperties,TcCRTdisplaysinvivoinhibitoryeffectsagainstanexperimentalmammarytumor.
Methodology and Principal Findings: TcCRT (or its N-terminal vasostatin-like domain, N-TcCRT) a) Abrogates capillary
growthintheexvivorataorticringassay,b)Inhibitscapillarymorphogenesisinahumanumbilicalveinendothelialcell
(HUVEC) assay, c) Inhibits migration and proliferation of HUVECs and the human endothelial cell line Eahy926. In these
assaysTcCRTwasmoreeffective,inmolarterms,thanHuCRT:d)Inconfocalmicroscopy,liveHUVECsandEAhy926cells,are
recognizedbyFITC-TcCRT,followedbyitsinternalizationandaccumulationaroundthehostcellnuclei,aphenomenonthat
isabrogatedbyFucoidin,aspecificscavengerre
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