Semaphorin-3D and Semaphorin-3E Inhibit the Development of Tumors from Glioblastoma Cells Implanted in the Cortex of the Brain 英文参考文献.docVIP

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Semaphorin-3D and Semaphorin-3E Inhibit the Development of Tumors from Glioblastoma Cells Implanted in the Cortex of the Brain 英文参考文献.doc

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Semaphorin-3D and Semaphorin-3E Inhibit the Development of Tumors from Glioblastoma Cells Implanted in the Cortex of the Brain 英文参考文献

Semaphorin-3DandSemaphorin-3EInhibitthe DevelopmentofTumorsfromGlioblastomaCells ImplantedintheCortexoftheBrain AdiD.Sabag1.,JuliaBode2.,DoritFink1.,BoazKigel1,WilfriedKugler2*,GeraNeufeld1* 1CancerResearchandVascularBiologyCenter,TheBruceRappaportFacultyofMedicine,Technion,IsraelInstituteofTechnology,Haifa,Israel,2DepartmentofPediatric HematologyandOncology,UniversityofGoettingen,Goettingen,Germany Abstract Class-3semaphorinsaresecretedaxonguidancefactors.Someofthesesemaphorinshaverecentlybeencharacterizedas suppressors of tumor progression. To determine if class-3 semaphorins can be used to inhibit the development of glioblastoma-multiformetumors,weexpressedrecombinantsema-3A,3B,3D,3E,3For3GinU87MGglioblastomacells. Sema3Aandsema3Bexpressingcellscontractedandchangedshapepersistentlywhilecellsexpressingothersemaphorins didnot.Sema3Aandsema3Fdifferedfromothersemaphorinsincludingsema3Bastheyalsoinhibitedtheproliferationof the cells and the formation of soft agar colonies. With the exception of sema3G and sema3B, expression of these semaphorins in U87MG cells inhibited significantly tumor development from subcutaneously implanted cells. Strong inhibitionoftumordevelopmentwasalsoobservedfollowingimplantationofU87MGcellsexpressingeachoftheclass-3 semaphorins in the cortex of mouse brains. Sema3D and sema3E displayed the strongest inhibitory effects and their expressioninU373MGorinU87MGglioblastomacellsimplantedinthebrainsofmiceprolongedthesurvivalofthemiceby more then two folds. Furthermore, most of the mice that died prior to the end of the experiment did not develop detectabletumorsandmanyofthemicesurvivedtotheendoftheexperiment.Mostofthesemaphorinsthatwehaveused herewiththeexceptionofsema3Dwerecharacterizedpreviouslyasinhibitorsofangiogenesis.Ourresultsindicatethat sema3Dalsofunctionsasaninhibitorofangiogenesisandsuggestthattheanti-tumorigeniceffectsaredueprimarilyto inhibition of tumor angiogenesis. These results indicate that class-3 semaphorins such as sema3D an