DOC

Lipids changes in liver cancer

By Alicia Nichols,2014-06-03 02:32
10 views 0
Lipids changes in liver cancerLipids

    Lipids changes in liver cancer

    398

    JournalofZhejiangUniversitySCIENCEB

    ISSN1673.1581(Print);ISSN18621783(Online)

    www.ziu.edu.cnus;wwwspringerlinkcom

    E-mail:JZUS@zjueducn

    eview:

    Jiangetal/JZhefiangUnivSciB20078(~:398?409

    Lipidschangesinlivercancer

    JIANGJingting,XUNing,ZHANGXiao.ying,WUChang.ping

    (1DepartmentofTumorBiologicalTreatment.theThirdAffiliatedHospital,SuzhouC,"n'ersit311Changzhou213003.China)

    (-,lnstttuteLaboratoO'Medicine.LtmdUnB,ersit).1S-22185Lund.''eden) E-mail:jjmew@163.com

    ReceivedJuly31,2006;revisionacceptedJan.23,2007

    Abstract:LiverisoneofthemostimportantorgansinenergYmetabolism.MostplasmaapoIipoproteinsandendogenouslipids

    andlipoproteinsaresynthesizedintheliver.Itdependsontheintegrityoflivercellularfunction.whichensureshomeostasisof

    lipidand1ipoproteinmetabolism.When1ivercanceroccurs.theseprocessesareimpairedandthep~,asmalipidandlipoprotein

    patternsmaybechanged.Livercanceristhefifthcommonmalignanttumorworldwide.andjscloselyrelatedtotheinfectionsof

    hepatitisBvirus(HBV)andhepatitisCvirusfHCV).HBVandHCVinfectionsarequitecommoninChinaandotherSoutheast

    Asiancountries.Inaddition.1ivercancerisoftenfollowedbyaprocessionofchronichepatitisorcirrhosis,sothathepaticfunction

isdamagedobviouslyonthesebases.whichmaysignificantlyinfluencelipidandlipoprotein

    metabolisminvivo.Inthisreview

    wesummarizetheclinicalsignificanceoflipidandlipoproteinmetabolismunderlivercancer

    .

    Keywords:Lipids,Lipoprotein,Livercancer doi:tO.163l~zus.2007.B0398Documentcode:ACLCnumber:R735.7 INTRoDUCTIoN

    TheliverisamajororganinenergYmetabolism. andplaysacriticalroleintheproductionmetabolism oflipidandlipoprotein,regulatingtheirsynthesisand degradation(Tietgeeta1.,1998);Liverfunctionde

    pendsontheintegratedactivityofdifierenthepatic cellsandtheinjuryoftheorgancouldresultindis

    integratedintracellularfunctions(Sherlock,l995); Changedlipidandlipoproteinmetabolismhomeo

    staticallyisoneofthefoundationsinvariousliver diseases,andisregulatedbyrelatedsubstances (LewisandRader,2005).Inadditionhepaticcells candrawhelpfromlipoproteinreceptorofthecells surfacetoabsorbandclearlipoproteinmetabolic products.Liverproducedlipoprotein,asmostof VLDL(verylowdensitylipoprotein)andpartofHDL (hidensitylipoprotein),andcouldkeepopposite balancedstateoflipidandlipoproteinmetabolismby thiswayinvivo(Pangburnet.198l1.

    Project(No.30570752)supportedbytheNationalNaturalScience FoundationofChina

    Mostplasmaproteinsandendogenouslipopro- teinsweresynthesizedinliver(Levi.1972;Alberset

    ,1977).butthesynthesisandsecretiondepended ontheintegrityofhepatocellularfunction(Eisenberg andLevy.1975).andisinfluencedbynormallipid andlipoproteinmetabolisminliverdiseasesrDavis andBryson.1994).

    Livercancerwasthefifthmalignanttumorinthe world(Parkineta1.,200l1,andwasinfectedwith hepatitisBvirus(HBV)andhepatitisCvirus(Hcv) whichwerecommoninChina(Shieta1.,2005), whichismajorremotecauseoflivercancer(Nissen andMartin,2002;Guaneta1..2004).Themortalityof livercancerwas20.4/100000inChina.occupied l8.8%ofallmalignanttumors.anditwasnextto gastriccanceronly.Comparedtoothercountriesjn theworldthemortalityoflivercancerinChinaoc

    cupiesthefirstplace(Zhangeta/.,l999).Theearlier periodoflivercancerisoftenfollowedbyhepatic cirrhosisprocesssothatliverfunctionisdamaged obviouslybyhepaticcirrhosis(SherlockandDooley l993),andinfluenceslipidnormalmetabolismin liver.Severeliverdiseasescoulddisorderlipoprotein

Jiangetal/JZhefiangUnivSciB20078(6):398409

    metabolismandchangelipidandlipoproteinlevelin serum(Cooperela1.,1996;Mottaela1.,2001;Ooiet a1.,2005).Inthisarticlewespeciallydiscussthe changesoflipidandlipoproteinandtheclinicalsig' nificancesinlivercancer.

    INFLUENCEOFLIVERCANCERoNTGME

    TABoLISM

    Patientswithlivercancerareoftenfclllowedby liverdiseases.Livercancerandchronicliverdisease influencebloodfatlevel(Cicognaniela1.,1997). Mottaeta1.(200l1detectedthattriglyceride(TG) leveldecreased28.8%in40caseswithlivercancer andthereductionofTGlevelsobservedintheirstudy seriesmaybeexplainedonthebasisoftherelation shipbetweencytokinesandlipids(Malaguarneraet ,..1994).LipidmetabolismproductssuchasTnf-c~. ILI.IL6.andIFNccareproducedbytumorcells

    (LangsteinandNorton.199l:Traceyeta1..1988).In factcytokinesinhibitedlipolysisfGiffordandLoh. mannMaRhes.1987).Hepaticcellsaredamaged simultaneouslyinhepatOcarcinOgenesisandinpa. tientswiththispattern,hepaticTGlipaseactivity significantlydecreasesfHiraokaela1..1993).TheX proteinofhepatitisBvirus(HBx)playsamajorrole inhepatocellularcarcinoma.ApolipoproteinB(apoB) intheliverisanimportantglycoproteinfortransport ofVLDLandlowdensitylipoproteinsfLDL).1nliver cellshyper-expressofHBxcausesnegativeaccom

    modationofmicrosomeTGtransferprotein,could increasetheexpressionofBdmannoside1,

    4NacetylglucosaminyltransferaseIIIfGnTIII).

    andcausesinhibitionofapoBsecretionandaccumu- IationofintracellularTGandcholesterolfTch)fKang Pfa1..2004).butserumTGlevelinlivercancerdid notobviouslydecreasecomparedwithlipoprotein(a) (Lp(a)),TchandHDL(Ooiela1.,2005).

INFLUENCEOFLIVERCANCERONCHOLES

    TEROLMETAB0LlSM

    Cholesterolmetabolismisanormalregulation processwhichfirsttransformedcholoicacidand desoxycholicacidthroughbiliarysysteminliver, thenasbilesaltwaspassedtobowelsthroughbiliary 399

    system(RothblatandPhillips.1986).Whenhepatic inadequacyoccuwedbecauseoflivercancerand chronicliverdiseaseform,esterificationand evacuationofcholesterolwereblocked,whichcauses changesofplasmacholesterollevelfCooperela1., 1996;Mottaeta1.,2001:Ooieta1.,2005;Heerenet a1.2004;Kanelela1.l983:Popescuela1.,2003); anditwasalsodiscoveredthatserumcholesterollevel wasnegativecorrelatedwithoccu~enceandmortal

    ityofsomecancersbyepidemiologicstudy(Lawand Thompson1991:Williamsela1.,1981).Studyofthe correlationbetweentotalserumcholesterolandtumor showedthatthecholesterollevelinpatientswhodied ofcancerwassignifcantlylowerthanthatinthose whosurvived(Cambieneta1..1980).

    Livercancerisawastingdisease.andwithpa

    tient'Sconditionprocess,tumorcellsproliferatedand neededtointakelargeamountofcholesterolasraw materialforcytomembranesynthesisrFunahashiel ,..1989).Tumorcellscholesterolintake.synthesis andchangesofmembranecontentsuggestedthat endogenouscholesterolmayplayanimportantrolein

tumorpathobiology(Dessieta1.,l994),andcholes

    terolmetabolicproductsparticipatedinduplicationof DNAandregulationofoncogeneproteinfCaseyela1.. 1989).

    Eightypercentageofendogenouscholesterolin serumissynthesizedinlivercellcytomicrosome fKrisans.1996).sincetherearecholesterolsynzymes incytomicrosomefGrfinlerela1.l995).Developing fromchronichepatitistolivercirrhosisresultedin reducedhepaticeellfibrosisandhydroxymethyl

    glutarylcoenzymeA(HMGCoA)reducasesynthesis. Withpatient'Sconditionaggravating.cholesterol synthesisinliverreducedandserumcholesterol contentgraduallydepressed,especiallyinlivercancer, whichexplainedthatserumcholesterolcontentde

    pressedsignificantlywhenpatient'Sconditionag

    gravatedandliverfunctionlesionintensified(0oiet a1.,2005:Coopereta1.,l996).

    ProteinkinaseC(PKC)ishypsoexpressedin

    livercancer.alsoisthemajormoleculeincellsignal transductionpathway,andplaysanimportantrolein cellgrowthandaggravation(Carter,2000).Incan

    cerizationoflivercellstheabnormalityofcellsignal transductionplaysakeyrole.andtheabnormalex

    pressionofPKCcciscloselycorrelatedwithgenesis anddevelopmentoflivercancerfTuP,a1.,200l:

    400Jiangotal/JZhejiangUnivSciB20078(6):398-409 Perlettieta1..1996).HDLreceptormediatedtrans

    locationandeffluxofintracellularcholesteroloccur

    throughactivationofPKC(Mendezeta1.,1991), whileactivationofPKCenhancesandinhibitionof PKCsuppressesapolipoproteinmediatedcholesterol

    efnuxfMendezeta1.,1991).HDLcausesserum cholesterolleveltosignificantlydecreaseinliver cancerfMottaeta1.,2001).

    CHANGEOFLIP0PR0TEININLIVERCANCER

    Liverisamajorsourceoftheendogenouslipo

    proteinsinvivo.meanwhile.anditisthemainsiteof thesynthesis,storage,transportanddegradationof lipidfLewisandRader,2005).Eachproteinisinflu

    encedbyliverdiseaseinadifferentwayandserum lipoproteinconcenl:rationswithfasterturnoverare

    morereducedwithrespecttothosewithslower turnover(Phillips,1960).

    MetabolismofLp(a)inlivercancer

    TheliveristhemainsiteofLp(a1synthesis (Malaguarneraeta1.,l994;1996;Kraftgta1.,1989). Intheviewofhealthycontrols,Lp(a)levelinliver cancerpatients'senlmstrikinglydecreasedcompared withthatofthenormalfSamonakiseta1.,2004),and itwasfoundLp(a1leveldecreasedinlivercancerand cirrhoticpatients.Lp(a)isproducedbytheliverandit isexpectedthatitslevelsmaydecreaseinpatients withchronicliverdiseasefSamonakiseta1.,2004). Thatliverplaysanimportantroleinlipidmetabolism andsoitisquitecertainthatamalfunctionofliver cellsmightinfluencesenlmLp(a1levels.Several factorssuchashormones,cytokines,geneticsand nutritionmaybeinvolvedindifferentway.witheach

    singleproteinbeingsynthetizedbytheliver(Phillips, l960).Severalinflammatoryandtumoraldiseasesare characterizedbytheproductionanddeliveryofcv

    tokinesinfluencingserllmLp(a)levels(Higuchieta1., 1988),soserumLp(a)issignificantlylowerinpa

    tientswithlivercancerfSamonakiseta1.,2004).The mechanismsbywhichthetumoursinducecachexia involveinflammatorycytokineproduction,whichis responsibleforawidenumberofmetabolicdisorders, essentiallyinvolvinglipidmetabolism(Langsteinand Norton,1991).SerumLp(a)levelchangesduring inflammatorydiseasefMaedaeta1.,1989);andalso liverdamageislinkedtoreducedLp(a)serumlevels fMalaguarneraeta1.,l996;Kostner,l983).Geisset df.(1996)longitudinallyobservedpatientsshowinga markedincreaseinLp(a)concentrationfrom7mg/dl inacutestageto32mg/dlinconvalescence,andacute hepatitisisassociatedwithdecreasedLp(a)serum levels.

    ObviousLp(a1half-lifeisbriefinvivo(3.3-3.9 d)(Kremplereta1.,1983),andinfluencedearlyby liverfunctionalterations(Malaguarneraeta1.,l994). ThenLp(a1issynthesizedandmetabolizedinde

    pendentlyofotherplasmalipoproteins,atthesame timetheserumLp(a1levelisnotinfluencedbyvari

    OUSdietarymanipulations(Alberseta1.,l977).Thus, Lp(a)isasubstanceinvolvedinlipidandproteic metabolism,andcanbeasensitiveandearlymarker oflivermalfunction.ItisconcludedthatLp(a)might

beusefulinthefollowupoflivercancerpatientsand

    thatferritinandccfetoproteincanbeusedforamore completeevaluationoftheliverfunction(Mottaeta1., 2001),foranalyzingtheLp(a)levelinvivo,andfor evaluatingtheliverfunctionalstatusofhepatoma patients(Malaguarneraeta1.,l996;Mottaeta1.,200l; Samonakiseta1.2004)buttheincreasedLp(a)se

    rumlevelwasfoundinhepatomapatientsfBasiliet /.,1997).

    MetabolismofHDLandLDLinlivercancer

    HDLcomprisesaheterogeneousmixtureof

    sphericalmacromoleculeswhichdifferinsize f80l20A)andchemicalcomposition;themain structuralproteinsareapoAI(apo"poproteinA1)

    andapoAII(apolipoproteinA11)(Assmannand

    Schriewer.1980).TheapoAlispresentonmost

    HDLparticlesandconstitutes70%oftheapolipo

    proteincontentofHDLparticles;itisnotonlythe structuralproteinofHDL.butalsotheactivatorof lecithincholesterolacyltransferase(LCAT1(Lewis andRader.2005).andmostHDLparticlescontain apoAlfKatsuramakieta1..2002).Difrerencesinthe quantitativeandqualitativecontentoflipids,apoli

    poproteins,enzymes,andlipidtransferproteinsre

    suitinthepresenceofvariousHDLsubclasses. whicharecharacterizedbydifferencesinshape. density,size,chargeandantigenicity(yonEckard

    steineta1..1994).

    ReversecholesteroltransportfRCT1isapath

    waytransportingcholesterolfromextrahepaticceils

    Jiangetal/dZhejiangUnivSciB20078(6).398-409 andtissuestotheliver.whichantiportprocessisde

    terminedatleastpartiallybytheHDLconcentration intheblood(SviridovandNestel,2002);HDLplays animportantroleincleaningthecholesterol(Fielding andFielding.1995).Cholesterolestertransferprotein (CETP)isanimportantdeterminantoflipoprotein function,especiallyHDLmetabolism,andcontrib

    utestotheregulationofplasmaHDLlevels(Hiranoet a1..2001).Therefore,HDLplaysakeyroleinthe reversecholesteroltransportpathwayinliver (Sviridoveta1.,l997;Genesteta1.,l990).Butwhen cellsareincubatedwithequivalentconcentrationsof isolatedlipoproteins.HDLismuchmoreeffectivein promotingl4CcholesteroleffluxthanLDL.

    suggestingthatunesterifiedcholesterolisinitially transfefredtoHDLandthentoLDLfSviridovand Fidge,1995),indicatingthattheprimarysiteofhu

    manHDLsynthesisisputativelyintheliver

    (Eggermaneta1.,l991;Garciaeta1.,1996).Inearlier periodoflivercanceritoftenfollowshepaticcirrhosis process.sothatliverfunctionisdamagedobviously byhepaticcirrhosis(SherlockandDooley.1993).Ooi a1.(2005analyzedlipidsinliverdiseasesbyaga

    rosegelelectrophoresis,anddifferentialstainingand simultaneousanalysisofthelipidandlipoprotein fractions,includingchronichepatitis(CH),livercir

    rhosis(LC),hepatocellularcarcinoma(HCC),and metastaticlivercancer.witheachfractionbeing

Report this document

For any questions or suggestions please email
cust-service@docsford.com