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Stem cells, cancer, and cancer stem cells

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Title: Stem cells, cancer, and cancer stem cells


1
Stem cells, cancer, andcancer stem cells
  • 113? lab seminar
  • ?? 1? ???

2
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

3
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

4
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

5
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6
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

7
(No Transcript)
8
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

9
Stem cells targets of Mutation
  • Proposed Cell-Surface Markers of the
  • Undifferentiated HSCs  

Mouse Human
CD34low- CD 34
SCA-1 CD59
Thy1low Thy1
CD38 CD38low-
C-kit C-kit -low
lin  lin
10
Progenitor cells as targets of transformation
11
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

12
Evidence for cancer stem cell
13
The implications of solid cancer stem cells
14
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

15
  • 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
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