神经节苷脂GM3与肿瘤

DOI:10.3971/j.issn.1000-8578.2011.01.033:2009-12-04;:2010-05-25:430022武汉,华中科技大学同济医学院附属协和医院肿瘤中心:伍钢,E-mail:[e-mail]:朱燕(1985-),女,硕士,主要从事非小细胞肺癌的研究GM3朱燕,伍钢:GM3;神经节苷脂;肿瘤:Q786;R73-3:A:1000-8578(2011)01-0112-030(ganglioside,GS),,[1]GM3,1952Yamakawa,a-Neu5Ac-(2-3)-B-Glc-(1-1)-Cer,GM3,GSGM3,GM3GSGS,,GM3GSGM3,,GS:GM3,GD3(disialoganglioside-3,GD3)GD1(disia-loganglioside-1,GD1)[2],GM3v-JunDF1GM3,GM3[3]GM3,[4]GM3,GM3GM3,,,,1GM3GM3,GM3BHK[5],(epidermalgrowthfactor,EGF)(epidermalgrowthfactorreceptor,EGFR),A431[6]Noll[7]GM3Mi-ljan[8]EGFRGM3LAID,GM3,EG-FR,EGFGM3EGFR,EGFEG-FR[9]EGFGM3EG-FR,GM3EGFREGFRN-GlcNAc[10]GM3,,GM3,GM3(GEM),[11]GM32GM3GM3,GM3,GM3,GM3GM3,2/3,GM350%(dendriticcells,DC)#112#2011381,DCGM3CD34+DCCD14+DC,GM3[12]GM3[13],,GM3GM3()GM3N--GM3Ñ,Ò[14],3GM3,GM3Neu3,Neu3GM3(Lac-cer),Neu3,GM3Lac-cer,,Bc-l2caspase[15]GM3,GM3caspase3,GM3,GM3-1,[16]GM3(Ò)TJurkat[17]GM3CD9CD82,,[18],4GM3,,,GM3(vascularendothelialgrowthfactor,VEGF)[19]Chung[20]GM3-2(vascu-larendothelialgrowthfactorreceptor-2,VEGFR-2),GM3VEGFGM3VEGFVEGFR-2,GM3VEGFR-2,VEGFR-2GM3VEGFVEGFR-2,GM3GM3VEGFR,GM3,,GM3,GM3GM3,,,GM3,GM35GM3Wang[21]MMPs,GM3PI3K/AktMMP-9Mitsuzuka[22]GM3CD9CD82,CD9CD82,GM3CD9CD82,GM3,GM3CD9,[22],GM3CD9,-5,GM36,,GM3,#113#2011381,:GM3GM3,,GM3,,GM3,,:[1]HakomoriS.Structure,organization,andfunctionofglyco-sphingolipidsinmembrane[J].CurrOpinHematol,2003,10(1):16-24.[2]MerzakA,KoochekpourS,PilkingtonGJ.Cellsurfacegan-gliosidesareinvolvedinthecontrolofhumangliomacellinva-sioninvitro[J].NeurosciLett,1994,177(1-2):44-46.[3]MiuraY,KainumaM,JiangH,etal.ReversionoftheJun-inducedoncogenicphenotypebyenhancedsynthesisofsialo-syllactosylceramide(GM3ganglioside)[J].ProcNatAcadSciUSA,2004,101(46):16204-16209.[4]ReginaTodeschiniA,HakomoriSI.Functionalroleofglyco-sphingolipidsandgangliosidesincontrolofcelladhesion,mo-tility,andgrowth,throughglycosynapticmicrodomains[J].BiochimBiophysActa,2008,1780(3):421-433.[5]ProkazovaNV,SamovilovaNN,GrachevaEV,etal.Gangl-iosideGM3anditsbiologicalfunctions[J].Biochemistry(MOSC),2009,74(3):235-249.[6]MeuilletEJ,Mania-FarnellB,GeorgeD,etal.ModulationofEGFreceptoractivitybychangesintheGM3contentinahu-manepidermoidcarcinomacellline,A431[J].ExpCellRes,2000,256(1):74-82.[7]NollEN,LinJ,NakatsujiY,etal.GM3asanovelgrowthregulatorforhumangliomas[J].ExpNeurol,2001,168(2):300-309.[8]MiljanEA,MeuilletEJ,Mania-FarnellB,etal.Interactionoftheextracellulardomainoftheepidermalgrowthfactorrecep-torwithgangliosides[J].JBiolChem,2002,277(12):10108-10113.[9]FujimotoY,IzumotoS,SuzukiT,etal.GangliosideGM3in-hibitsproliferationandinvasionofglioma[J].JNeurooncol,2005,71(2):99-106.[10]SottocornolaE,BerraB,ColomboI,etal.GM3contentmodulatestheEGF-activatedp185c-neulevels,butnotthoseoftheconstitutivelyactivatedoncoproteinp185neu[J].Bio-chimBiologysActa,2003,1635(2-3):55-66.[11]OnoM,HakomoriS.Glycosylationdefiningcancercellmotil-ityandinvasiveness[J].GlycoconjJ,2003,20(1):71-78.[12]WÊlflM,BattenWY,PosovszkyC,etal.Gangliosidesinhib-itthedevelopmentfrommonocytestodendriticcells[J].ClinExpImmunol,2002,130(3):441-448.[13]BennaceurK,PopaI,ChapmanJA,etal.Differentmecha-nismsareinvolvedinapoptosisinducedbymelanomaganglio-sidesonhumanmonocyte-deriveddendriticcells[J].Glycob-iology,2009,19(6):576-582.[14]GuthmannMD,CastroMA,CinatG,etal.Cellularandhu-moralimmuneresponsetoN-Glycoly-lGM3elicitedbypro-longedimmunotherapywithanant-iidiotypicvaccineinhigh-riskandmetastaticbreastcancerpatients[J].JImmunother,2006,29(2):215-223.[15]AnastasiaL,PapiniN,ColazzoF,etal.NEU3sialidasestrictlymodulatesGM3levelsinskeletalmyoblastsC2C12thusfavoringtheirdifferentiationandprotectingthemfromapoptosis[J].JBiolChem,2008,283(52):36265-36271.[16]BassiR,VianiP,GiussaniP.GM3gangliosideinhibitsendo-thelin-1-mediatedsignaltransductioninC6gliomacells[J].FEBSLett,2001,507(1):101-104.[17]AzumaY,SatoH,HigaiK,etal.Enhancedexpressionofmembrane-associatedsialidaseNeu3decreasesGD3andincrea-sesGM3onthesurfaceofJurkatcellsduringetoposide-in-ducedapoptosis[J].BiolPharmBull,2007,30(9):1680-1684.[18]WangXQ,YanQ,SunP.SuppressionofepidermalgrowthfactorreceptorsignalingbyproteinkinaseC-Aactivationre-quiresCD82,caveolin-1,andganglioside[J].CancerRes,2007,67(20):9986-9995.[19]MukherjeeP,FaberAC,SheltonLM,etal.Thematicreviewseries:sphingolipids.gangliosideGM3suppressestheproan-giogeniceffectsofvascularendothelialgrowthfactorandgan-gliosideGD1a[J].JLipidRes,2008,49(5):929-938.[20]ChungTW,KimSJ,ChoiHJ,etal.GangliosideGM3inhib-itsVEGF/VEGFR-2-mediatedangiogenesis:DirectinteractionofGM3withVEGFR-2[J].Glycobiology,2009,19(3):229-239.[21]WangY,YamaguchiK,WadaT,etal.Acloseassociationoftheganglioside-specificsialidaseNeu3withcaveolininmem-branemicrodomains[J].JBiolChem,2002,277(29):26252-26259.[22]MitsuzukaK,HandaK,SatohM,etal.Aspecificm-icrodomain(/Glycosynapse30)controlsphenotypicconversionandreversionofbladdercancercellsthroughGM3-mediatedinteractionofA3B1integrinwithCD9[J].JBiolChem,2005,280(42):35545-35553.[:周永红;:刘红武]#114#2011381