Slit2-Robo1在腫瘤新生血管中的功能研究以及Robo1在正常細(xì)胞向腫瘤細(xì)胞轉(zhuǎn)化過(guò)程中的功能研究.pdf

1、中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所博士學(xué)位論文Slit2Robo1在腫瘤新生血管中的功能研究以及Robo1在正常細(xì)胞向腫瘤細(xì)胞轉(zhuǎn)化過(guò)程中的功能研究姓名：肖洋申請(qǐng)學(xué)位級(jí)別：博士專業(yè)：細(xì)胞生物學(xué)指導(dǎo)教師：耿建國(guó)20060814AbstractSlitisaknownsecretedneuronguidancecue，andfunctionsasthechemorepellentinaxonguidanceandneuro

2、nalmigrationandasarlinhibitorinleukocytechemotaxisHereourexpefimmHsshowedSlit2expressionsinalargenumberoftumorcelllinesanditsreceptorRobolexpressionsinhumanembryonicveinendothelialcellsRecombinantSlit2proteinattractedend

3、othelialcellsmigrationandpromotedmbeformationinaRobo1一andphosphatidylinositolkinasedependemmanner。InCAMassayantiRobolfunctionblockingmAbcouldinhibitcapillaryfbrmationinthechickenatlantoicmembraneInnudemiceXenograftassayw

4、efoundthetumorinducedbySlit2／A375cells，whichoverexpressedSlit2proteingrewmuchfasterburdenedmoremicrovesselandbiggertumormassthanthecontrolv／A375cells。BothRoboN(Rob01extracellularregion)andantiRobolfunction—blockingmAbcou

5、ldslowerthegro姒hrateoftumorinduced姆A375cells，decreasethemicrovesseldensRyandthetumormassAtlthesefindingsdemonstrate獺eangiogentieroleofSlit2／Robo1signalpathwayintumorandassociatedpositiveeffectontumorgrowthIntheresearchof

6、Slit2／RoboIsignalpathwaywealsofoundFilamin—A，acytoskeletonpmtein，andbindingtobolCC3domain，hadthepossibilitytOtakepartinthesignalpathwaydovmstreamofSlit2／RoboI。Roboloverexpressioninhtunanembryonickidney293celllinecouldcha

7、ngethecellshape，increasetheproliferationandmigrationabilityofcellinvitro，andalsoinducenonnalcellstransformation鏹Rlmorceilstbroughdown—regulationofE。cadherinRoboU293cellscouldpromotetumorandmetastasisinlungandliverinmillm