Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels 英文参考文献.docVIP

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Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels 英文参考文献.doc

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Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels 英文参考文献

AlterationofCellularBehaviorandResponsetoPI3K PathwayInhibitionbyCulturein3DCollagenGels BrianFallica1,JosephS.Maffei1,ShaunVilla2,GuyMakin2,3,MuhammadZaman1* 1Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America, 2Clinical and Experimental Pharmacology, Paterson Institute for Cancer Research, and School of Cancer and Enabling Sciences, Manchester Cancer Research Centre and Manchester Academic Health Sciences Centre, UniversityofManchester,Manchester,UnitedKingdom,3DepartmentofPaediatricOncology,RoyalManchesterChildren’sHospital,Manchester,UnitedKingdom Abstract Most investigations into cancer cell drug response are performed with cells cultured on flat (2D) tissue culture plastic. Emergingresearchhasshownthatthepresenceofathree-dimensional(3D)extracellularmatrix(ECM)iscriticalfornormal cellbehaviorincludingmigration,adhesion,signaling,proliferationandapoptosis.Inthisstudyweinvestigatedifferences betweencancercellsignalingin2Dcultureanda3DECM,employingreal-time,livecelltrackingtodirectlyobserveU2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the importantPI3Ksignalingpathwayunderthesedifferentgrowthconditionsisstudied,andtheresponsetoinhibitionofboth PI3KandmTORwithPI103investigated.Cellsgrownin3Dgelsshowreducedproliferationandmigrationaswellasreduced PI3Kpathwayactivationwhencomparedtocellsgrownin2D.OurresultsquantitativelydemonstratethatacollagenECM canprotectU2OScellsfromPI103.Overall,ourdatasuggeststhat3Dgelsmayprovideabettermediumforinvestigationof anti-cancerdrugsthan2Dmonolayers,thereforeallowingbetterunderstandingofcellularresponseandbehaviorinnative likeenvironments. Citation:FallicaB,MaffeiJS,VillaS,MakinG,ZamanM(2012)AlterationofCellularBehaviorandResponsetoPI3KPathwayInhibitionbyCulturein3DCollagen Gels.PLoSONE7(10):e48024.doi:10.1371/journal.pone.0048024 Editor:HidayatullahG.Munshi,NorthwesternUniversity,UnitedStatesofAmerica ReceivedJuly5