Aldehyde Dehydrogenase 1, a Potential Marker for Cancer Stem Cells in Human Sarcoma 英文参考文献.docVIP

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Aldehyde Dehydrogenase 1, a Potential Marker for Cancer Stem Cells in Human Sarcoma 英文参考文献.doc

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Aldehyde Dehydrogenase 1, a Potential Marker for Cancer Stem Cells in Human Sarcoma 英文参考文献

AldehydeDehydrogenase1,aPotentialMarkerfor CancerStemCellsinHumanSarcoma BirgitLohberger1*,BeateRinner2,NicoleStuendl1,MarkusAbsenger2,BernadetteLiegl-Atzwanger3, SonjaM.Walzer4,ReinhardWindhager4,AndreasLeithner1 1Department ofOrthopaedicSurgery,Medical University of Graz, Graz, Austria, 2Center for Medical Research, MedicalUniversity ofGraz, Graz, Austria, 3Institute of Pathology,MedicalUniversityofGraz,Graz,Austria,4DepartmentofOrthopaedicSurgery,MedicalUniversityofVienna,Vienna,Austria Abstract Tumors contain a small population of cancer stem cells (CSC) proposed to be responsible for tumor maintenance and relapse. Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate CSCs in differentcancertypes.ThisstudyusedtheAldefluorHassayandfluorescence-activatedcellsorting(FACS)analysistoisolate ALDH1high cellsfromfivehumansarcomacelllinesandoneprimarychordomacellline.ALDH1high cellsrangefrom0.3% (MUG-Chor1)to4.1%(SW-1353)ofgatedcells.Immunohistochemicalstaining, analysisofthecloneformationefficiency, and xCELLigence microelectronic sensor technology revealed that ALDH1high cells from all sarcoma cell lines have an increasedproliferationratecomparedtoALDH1lowcells.Byinvestigatingofimportantregulatorsofstemcellbiology,real- time RT-PCR data showed an increased expression of c-Myc, b-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1lowcells.Thisstudydemonstratesthatindifferentsarcomacelllines,highALDH1activitycanbeusedtoidentifya subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expressionofABCtransportergenesandstemnessmarkerscomparedtocontrolcells.Inaddition,enhanceddrugresistance wasdemonstrated. Citation: