FTY720 Suppresses Liver Tumor Metastasis by Reducing the Population of Circulating Endothelial Progenitor Cells 英文参考文献.doc

FTY720SuppressesLiverTumorMetastasisbyReducing thePopulationofCirculatingEndothelialProgenitor Cells ChangXianLi,YanShao,KevinT.P.Ng,XiaoBingLiu,ChangChunLing,YuenYuenMa,WeiGeng, SheungTatFan,ChungMauLo,KwanMan* DepartmentofSurgery,CentreforCancerResearchandStateKeyLaboratoryofLiverResearch,TheUniversityofHongKong,HongKong,China Abstract Background: Surgical procedures such as liver resection and liver transplantation are the first-line treatments for hepatocellularcarcinoma(HCC)patients.However,thehighincidenceoftumorrecurrenceandmetastasisafterliversurgery remains a major problem. Recent studies have shown that hepatic ischemia-reperfusion (I/R) injury and endothelial progenitorcells(EPCs)contributetotumorgrowthandmetastasis.WeaimtoinvestigatethemechanismofFTY720,which wasoriginallyappliedasanimmunomodulator,onsuppression oflivertumormetastasisafterliverresectionandpartial hepaticI/Rinjury. Methodology/PrincipalFindings:AnorthotopiclivertumormodelinBuffaloratwasestablishedusingthehepatocellular carcinomacelllineMcA-RH7777.Twoweeksafterorthotopiclivertumorimplantation,theratsunderwentliverresectionfor tumor-bearinglobeandpartialhepaticI/Rinjury.FTY720(2mg/kg)wasadministeredthroughtheinferiorcavalveinbefore and after I/R injury. Blood samples were taken at days 0, 1, 3, 7, 14, 21 and 28 for detection of circulating EPCs (CD133+CD34+).Ourresultsshowedthatintrahepaticandlungmetastasesweresignificantlyinhibitedtogetherwithless tumor angiogenesis by FTY720 treatment. The number of circulating EPCs was also significantly decreased by FTY720 treatmentfromday7today28.HepaticgeneexpressionsofCXCL10,VEGF,CXCR3,CXCR4inducedbyhepaticI/Rinjury weredown-regulatedinthetreatmentgroup. Conclusions/Significance:FTY720suppressedlivertumormetastasisafterliverresectionmarredbyhepaticI/Rinjuryina ratlivertumormodelbyattenuatinghepaticI/RinjuryandreducingcirculatingEPCs. Citation:LiCX,ShaoY,NgKTP,LiuXB,LingCC,etal.(2012)FTY720SuppressesLiverTumorMetastasisbyReducingthePopulationofC