Role of Stem Cells in Human Uterine Leiomyoma Growth 英文参考文献.docVIP

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Role of Stem Cells in Human Uterine Leiomyoma Growth 英文参考文献.doc

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Role of Stem Cells in Human Uterine Leiomyoma Growth 英文参考文献

RoleofStemCellsinHumanUterineLeiomyomaGrowth MasanoriOno,WenanQiang,VanidaAnnSerna,PingYin,JohnS.CoonV,AntoniaNavarro, DianaMonsivais,ToshiyukiKakinuma,MatthewDyson,StacyDruschitz,KenjiUnno,TakeshiKurita, SerdarE.Bulun* DivisionofReproductiveBiologyResearch,DepartmentofObstetricsandGynecology,FeinbergSchoolofMedicineatNorthwesternUniversity,Chicago,Illinois,United StatesofAmerica Abstract Background: Uterine leiomyoma is the most common benign tumor in reproductive-age women. Each leiomyoma is thoughttobeabenignmonoclonaltumorarisingfromasingletransformedmyometrialsmoothmusclecell;however,itis notknownwhatleiomyomacelltypeisresponsiblefortumorgrowth.Thus,wetestedthehypothesisthatadistinctstem/ reservoir cell-enriched population, designated as the leiomyoma-derived side population (LMSP), is responsible for cell proliferationandtumorgrowth. PrincipalFindings:LMSPcomprisedapproximately1%ofallleiomyomaand2%ofallmyometrium-derivedcells.AllLMSP and leiomyoma-derived main population (LMMP) but none of the side or main population cells isolated from adjacent myometriumcarriedamediatorcomplexsubunit12mutation,ageneticmarkerofneoplastictransformation.Messenger RNA levels for estrogen receptor-a, progesterone receptor and smooth muscle cell markers were barely detectable and significantlylowerintheLMSPcomparedwiththeLMMP.LMSPalonedidnotattachorsurviveinmonolayercultureinthe presenceorabsenceofestradiolandprogestin,whereasLMMPreadilygrewundertheseconditions.LMSPdidattachand survive when directly mixed with unsorted myometrial cells in monolayer culture. After resorting and reculturing, LMSP gainedfullpotentialofproliferation.Intriguingly,xenograftscomprisedofLMSPandunsortedmyometrialsmoothmuscle cellsgrewintorelativelylargetumors(3.6761.07mm3),whereasxenograftscomprisedofLMMPandunsortedmyometrial smoothmusclecellsproducedsmallertumors(0.5460.20mm3,p,0.05,n=10pairedpatientsamples).LMSPxenografts displayedsignificantlyhigherproliferativeactivitycomparedwithLMMPxenografts(p,0.0