肿瘤干细胞临床一对郑楠薪刘泓毅刘洋.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,FUNDAMENTAL,QUESTIONS,What makes the 200 cell types in our body remember their identity?,Whats the relationship between stem cells and CSC?,Do we have any ways in horizon to conquer cancer?,The Definition of Stem Cells,Stem cells are defined as cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue through differentiation.In most tissues,stem cells are rare.,Tannishtha Reya,Sean J.Morrison,Michael F.Clarke and Irving L.Weissman.,Nature,414,105-111，2001,Development of haematopoietic stem cells,CLP:common lymphoid progenitors,CMP:common myeloid progenitors,GMP:granulocyte macrophage precursors,MEP:megakaryocyte erythrocyte precursor,MkP:megakaryocyte precursors,ErP:erythrocyte precursor,Two general models of heterogeneity in solid cancer of cells,Stem cells and Tumor cells,The similarities in the mechanisms that regulate self-renewal of,normal stem cells,and,cancer cells,The possibility that tumor cells might arise from normal stem cells,The notion that tumors might contain,cancer stem cells,(SCS),Concept of cancer stem cells,Cancer stem cells have been defined as a cell within a tumor that possess(sic)the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor(Clarke et al,2006).,Property,Definition,Assay,Self-renewal,The ability to undergo symmetric division,Re-plating assays,And thereby indefinitely replenish itself,Serial transplantation,Differentiation,capacity,The ability to undergo asymmetric division and thereby recapitulate all tumor cell types,Differentiation,Transplantation,Tumor initiation,Metastasis,Relapse,The ability to propagate tumor when transplanted into the proper environment,The ability of resistance to different therapies and the ability to relapse,Sphere formation,Invasion assays,Transplantation,Chemo/radio-resistance,assays,Cancer Stem Cell Properties,Evidence for Cancer Stem Cells,1.1/10000 to 1/100 cancer cells from mouse myeloma cells formed colonies,and 1-4%of leukamia cell formed in vivo spleen colonies.(Park,CH,et al.J.Natl.Cancer Inst,46:411-422,1971,2.CD34+CD38-cells from human AML patients induced serial transplatation in NOD/SCID mice in 1/10,6,.(Bonnet and Dick,Nat Med,1997,3:730,Guan,XY.,et al.Gastroenterology,2007,132(7):2542-2556,Figurative depiction of the landscape of somatic mutations present in a single cancer genome,The cancer genome.Nature.2009，458(7239):719,Lung cancer cell line NCI-H2171,Int J Biochem Cell Biol.2011,43(2):265-70.,Mutations and deletions in the N-terminal domain of-catenin in hepatoblastoma,Clark and Fuller.Cell,2006,124(6):1111-1115,Niche and stem cells,Maintains and regulates stem cells,British Journal of Cancer,(2010),103,439445,Cancer stem cell theory of tumor development and relapse initiation,Stem cells,progenitors,Differentiated cells,Undifferentiated cells,Cancer stem cells,Tumors,Cancer progenitor cells,Cancer stem cells,Oncogenic events,Genetic/epigenetic events,?,?,Conventional therapies may shrink tumours by killing mainly cells with limited proliferative potential,Tannishtha Reya,Sean J.Morrison,Michael F.Clarke and Irving L.Weissman.,Nature,414,105-111(1 November 2001),targeted therapy of CSC,JCI,120:41-50,2010,JCI,120:41-50,2010,targeted therapy of CSC,Thank You,