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What makes the 200 cell types in our body remember their identity?
What’s 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/ 106.(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