Stem cells, cancer, andcancer stem cells

113 회 lab seminar석사 1 년 신호수

Stem cells?

Stem cells are defined as cells that have theability to perpetuate themselves throughself-renewal and to generate mature cells ofa particular tissue through differentiation. Inmost tissues, stem cells are rare. As a result,stem cells must be identified prospectivelyand 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 sel

f-renewal potential

Stem self-renewal Versus Oncogenesis

※ Many pathways are associated with cancer may also regulated normal stem cell development

1.Bcl-22.Bmi13.Notch 4.Sonic hedgehog(Shh)5.Wnt signalling

Self-renewal and Leukaemogenesis

If stem cell self-renewal lead totumorgenesis then are stem cells themselvesthe target of transformation in certain typesof cancer?1.Stem cells have the machinery for self-renewa

l already activated2.By self-renewing, stem cells often persist for l

ong period of time

Stem cells targets of Mutation

Proposed Cell-Surface Markers of the

Undifferentiated HSCs

Mouse Human

CD34low- CD 34+

SCA-1+ CD59+*

Thy1+low Thy1+

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 cellsgive rise to phenotypically heterogenouscells that exhibit various degrees ofdifferentiation Thus, tumorgenic cells can be thought ofanalogous 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 cell

s that can self-renew indefinitely, in contrast…

8.Necessary to identify and kill the cancer cell