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1、InducingAngiogenesis诱导血管生产Likenormaltissues,tumorsrequiresustenance（食物）intheformofnutrientsandoxygenaswellasanabilitytoevacuatemetabolicwastesandcarbondioxide.Thetumor-associatedneovasculature,generatedbytheprocessofangiogenesis,addressestheseneeds.Duringembryogenesis,thedevelopmentof
2、thevasculatureinvolvesthebirthofnewendothelialcellsandtheirassemblyintotubes(vasculogenesis)inadditiontothesprouting(angiogenesis)ofnewvesselsfromexistingones.Followingthismorphogenesis,thenormalvasculaturebecomeslargelyquiescent.Intheadult,aspartofphysiologicprocessessuchaswoundheali
3、ngandfemalereproductivecycling,angiogenesisisturnedon,butonlytransiently.Incontrast,duringtumorprogression,an‘‘angiogenicswitch’’isalmostalwaysactivatedandremainson,causingnormallyquiescentvasculaturetocontinuallysprout（萌芽）newvesselsthathelpsustainexpandingneoplasticgrowths(Hanahanand
4、Folkman,1996).就像其他正常的细胞一样，肿瘤需要营养供应，需要养分，同时也需要清除代谢垃圾和二氧化碳。肿瘤相关的血管生成保证了肿瘤的这一个特点。在胚胎形成过程中，血管的生存需要产生新的内皮细胞，然后将这些内皮细胞移入到小管当中，这一过程能促进新兴血管的表达。人体的血管系统基本上是静止的。在成年人当中，比如伤口愈合或者女性月经周期中，也会有新的血管生成，但是，这些血管产生只是一过性的。然而，在肿瘤形成过程中，血管生成按钮持续性的被激活，而且一直保持激活的状态，导致静止的静脉形成转化为持续性的血管生成，从而保证肿瘤的血供。Acompellingbodyof
5、evidenceindicatesthattheangiogenicswitchisgovernedbycountervailingfactorsthateitherinduceoropposeangiogenesis(BaeriswylandChristofori,2009;BergersandBenjamin,2003).Someoftheseangiogenicregulatorsaresignalingproteinsthatbindtostimulatoryorinhibitorycellsurfacereceptorsdisplayedbyvascul
6、arendothelialcells.Thewell-knownprototypesofangiogenesisinducersandinhibitorsarevascularendothelialgrowthfactor-A(VEGF-A)andthrombospondin-1(TSP-1),respectively.TheVEGF-Ageneencodesligandsthatareinvolvedinorchestratingnewbloodvesselgrowthduringembryonicandpostnataldevelopment,andtheni
7、nhomeostaticsurvivalofendothelialcells,aswellasinphysiologicalandpathologicalsituationsintheadult.VEGFsignalingviathreereceptortyrosinekinases(VEGFR-1–3)isregulatedatmultiplelevels,reflectingthiscomplexityofpurpose.Thus,VEGFgeneexpressioncanbyupregulatedbothbyhypoxiaandbyoncogenesignal
8、ing(F
