Stem cells, cancer, and cancer stem cells 113 회 lab seminar 석사 1 년 신호수

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. As a result, stem cells must be identified prospectively and purified carefully

Focus on three aspects of the relationship between stem cells and tumour cells 1.The similarities in the mechanisms that regulate self-renewal of normal stem cells and cancer cells 2.The possibility that tumour cells might arise from normal stem cells 3.The notion tumours might contain ‘cancer stem cells’

Self-renewal of haematopoietic stem cell ※ Three different populations 1.Long-term self-renewing HSCs, 2.Short-term self-renewing HSCs, 3.Multipotent progenitors without detectable self-renewal potential

Stem self-renewal Versus Oncogenesis ※ Many pathways are associated with cancer may also regulated normal stem cell development 1.Bcl-2 2.Bmi1 3.Notch 4.Sonic hedgehog(Shh) 5.Wnt signalling

Self-renewal and Leukaemogenesis If stem cell self-renewal lead to tumorgenesis then are stem cells themselves the target of transformation in certain types of cancer? 1.Stem cells have the machinery for self- renewal already activated 2.By self-renewing, stem cells often persist for long period of time

Stem cells targets of Mutation Proposed Cell-Surface Markers of the Undifferentiated HSCs MouseHuman CD34low-CD 34+ SCA-1+CD59+* Thy1+lowThy1+ CD38+CD38low- C-kit+C-kit -low lin* lin **

Progenitor cells as targets of transformation

Cancer stem cells and aberrant organogenesis Both normal stem cells and tumorgenic cells give rise to phenotypically heterogenous cells that exhibit various degrees of differentiation Thus, tumorgenic cells can be thought of analogous to what normal stem cells do

Evidence for cancer stem cell

The implications of solid cancer stem cells

Summary & Perspective 1.Self renewal is the hallmark property of stem cells in normal and neoplastic tissue 2. In the haematipoietic system, long-term self renewal is limited to rare long-term HSCs and some lymphocyte 3.Cells that continue to devide over long periods of time are much more likely to accumulate mutations 4.Normal tissues contain self-renewing stem cells

5.Distinct signalling pathways control stem cell renewal in different tissues 6.Understanding the signalling pathways.. 7.Most tumors there may exist cancer stem cells that can self-renew indefinitely, in contrast… 8.Necessary to identify and kill the cancer cell