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Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line

Cell.Mol.LifeSci.(2010)67:3915–3925DOI10.1007/s00018-010-0420-9

CellularandMolecularLifeSciences

RESEARCHARTICLE

Identi cationofcancerstemcell-likecellsfromhumanepithelialovariancarcinomacellline

M.F.Shi J.Jiao W.G.Lu F.Ye D.MaQ.G.Dong X.Xie

Received:4January2010/Revised:23April2010/Accepted:25May2010/Publishedonline:12June2010ÓSpringerBaselAG2010

AbstractCancerstemcells(CSCs)playanimportantroleinthedevelopment,invasion,anddrugresistanceofcarci-noma,buttheexactphenotypeandcharacteristicsofovarianCSCsarestilldisputable.Inthisstudy,weidenti edcancerstemcell-likecells(CSC-LCs)andinvestigatedtheircharacteristicsfromtheovarianadenocarcinomacellline3AO.OurresultsshowedthatCSC-LCswereenrichedinsphere-formingtestandhighlyexpressedCD44?CD24-.ThespheresandCD24-cellspossessedstrongtumorigenicabilitybytransplantationintononobesediabetic/severecombinedimmunode cientmice.CD44?CD24-cellsexpressedstemcellmarkersanddifferentiatedtoCD44?CD24?cellsbyimmuno uorescenceassayand uorescence-activatedcell-sortinganalysis.Invitroexper-imentsveri edthatCD44?CD24-cellsweremarkedlyresistanttocarboplatinandpaclitaxol.Inconclusion,ourstudyidenti estheCD44?CD24-phenotype,self-renewal,hightumorigenicity,differentiationpotential,anddrugresistanceofovarianCSC-LCs.Our ndingsmayprovide

theevidenceneededtoexploreanewstrategyinthetreatmentofovariancancer.

KeywordsCancerstemcellsÁOvariancarcinomaÁCD44ÁCD24

Introduction

Ithasbeenassumedthatasmallsubsetofcancercells,calledcancerstemcells(CSCs),constituteareservoirofself-sustainingcellswiththeexclusiveabilitytoself-renewandmaintainthetumor[1].ResearchofCSCshasachievedremarkableresultsoverthepastseveralyears.Firstlydemonstratedinacutemyeloidleukemia[2],cancerstemcell-likecells(CSC-LCs)havebeenidenti edinseveralsolidtumorsincludingbreast[3],brain[4],prostatetumors[5],andothers.Fivekeycriteriaclassicallyde nedtheexistenceofCSCstodate:(1)aminorityofthetumorpopulation,(2)thecapacitytoself-renew,(3)multipotentdifferentiationintonontumorigeniccells,(4)expressionofdistinctivecellsmarkers,and(5)tumorigenicpotentialtorecreatethefullphenotypicheterogeneityoftheparenttumor[1,6–9].AseriesofCSCstudiesindicatethatCSCsmaybetheprimarysourceleadingtothegenesis,devel-opment,invasion,metastasis,recurrence,anddrugresistanceofcancers[1,3,10–13].

Ovariancanceristhemostlethalmalignancyinthefemalereproductivesystem.Morethan80%ofpatientspresentwithadvanceddiseaseatthe rstdiagnosis,with5-yearsurvivalratesbetween15and45%[14].Epithelialovariancarcinoma(EOC)accountsforapproximately90%ofhumanovariancancer.ThehighpercentageofrecurrenceorchemoresistanceisthebiggestprobleminthetreatmentofEOCtoday.InafewstudiesonovarianCSCs,Bapatand

M.F.ShiÁJ.JiaoÁW.G.LuÁF.YeÁX.Xie(&)

DepartmentofGynecologicOncology,Women’sHospital,SchoolofMedicine,Women’sReproductiveHealthLaboratoryofZhejiangProvince,ZhejiangUniversity,2XueshiRoad,Hangzhou,Zhejiang,Chinae-mail:[email protected]://www.hjavira.net

Q.G.Dong(&)

ShanghaiCancerInstitute,ShanghaiJiaoTongUniversity,2200XietuRoad,Shanghai,Chinae-mail:[email protected]://www.wenkuxiazai.com

D.Ma

CancerBiologyResearchCenter,

TongjiHospital,TongjiMedicalCollege,

HuazhongUniversityofScienceandTechnology,Wuhan,Hubei,China

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