1. Cancer Stem Cell Xie Li & Li Rutian

3. Beginning of the Cancer Stem Cell Concept  1937: Jacob Furth and Morton Kahn: a single leukaemic cell was able to transmit the systemic disease when transplanted into a mouse.  1960s: Robert Bruce and Hugo Van der Gaag: only a small subset of primary cancer tissue was able to proliferate in vivo.  Not every cell is able to proliferate to form a colony in vitro or to give rise to a tumor when transplanted in vivo.

4. Definition  A CSC is a cancer cell that has the ability to self-renew; dividing to give rise to another malignant stem cell and a cell that gives rise to the phenotypically diverse tumour cell population. Enriched for tumorigenic ability. Enable serial propagation in vivo. Regenerate phenotype diversity (differentiation)

6. Metastasis CXCR4

7. CSC in solid tumors  BREAST CANCER:  CD44 + CD24 -/low ESA + Cells

8. Identification of CSCs  Prospective purification using cell surface markers followed by tumorigenic assays.  FACS ( Fluorescence-Activated Cell Sorting ) enrichment of side populations.

9. Ex vivo and in vivo assays for tumor cells

10. Markers of Normal and Malignant Adult Tissue Stem Cells OrganNormal TissueCancer Hematopoietic CD34 + CD38 - Thy1 + c-kit + IL-3R  - CD34 + CD38 - Thy1 - c-kit - IL-3R  + Breast Lin - Sca1 low CD24 med CD49f high OR Lin - CD29 hi CD24 + CD44 + CD24 -/low Lineage - Brain CD133 + Lung Sca-1 + CD34 + Skin CD20 + Prostate CD44 + /  2  1 hi /CD133 +

11. SPs C6 Glioma MCF7 breast Cancer B104 neuroblastoma Hela Side Population hoechst33342

12. Orignation of CSCs  Adult or Embryonic Stem Cells that turn malignant?  Malignant Cells that display “ stem-like ” property?

13. Orignation of CSCs Cell–cell fusion Horizontal gene-transfer

14. Special Signaling Pathways

15. NICHE  Microenvironmental cells that nurture stem cells and enable them to maintain tissue homeostasis

16. NICHE  primarily inhibitory signals for both proliferation and differentiation  transient signals for stem cell division to support ongoing tissue regeneration  proliferation-inhibiting proliferation-promoting

17. Reciprocal interactions between CSC and Niche

18. Vascular niche

19. NICHE-----signaling  SDF1-----------o(∩_∩)o  MMP-9-----------(*^__^*)

20. CSCs and drug-resistance  cell cycle kinetics  DNA replication and repair mechanisms  antiapoptotic proteins  transporter proteins  antigen

21. Strategies  Prinncipally, there are therefore two strategies to be considered for CSC cancer therapies: exposure of CSCs to sufficiently high levels  Drug delivery  Inhibition of drug pump the development of novel therapeutic agents that are targeted to CSCs.  Wnt  Pten  Her1/Her2  Differentiation induction Niche as the targets  Anti-angiogenesis

23. Thank You o( ∩ _ ∩ )o