Cancer stem cells Flashcards

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1
Q

What are the two essential properties of stem cells?

A
  • self renewal
  • differentiation into specialised cells
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2
Q

What do haematopoetic stem cells differentiate into?

A
  • myeloid or lymphoid progenitors
  • RBCs, platelets etc
  • immune cells
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3
Q

What is replicative senescense?

A

each differentiated cell divides a certain number of times before it undergoes apoptosis

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4
Q

What is the ratio of cell birth to cell death?

A
  • usually equal
  • becomes unbalanced in cancer
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5
Q

Define
- benign
- malignant
- metastatic

A
  • non-invasive
  • locally invasive
  • spread to other organs or tissues
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6
Q

What is clonal expansion?

A
  • multiplication of specific cells
  • rapid amplification
  • clones of this cell grow and live with the normal cells
  • clones acquire further mutations to form new clones with more survival advantage
  • can lead to malignancy + metastasis if cells with these properties are amplified
  • one cell acquires a mutation that gains a selective advantage
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7
Q

What are 4 factors that cause cancer?

A
  • viruses
  • muatations in specific genes
  • breakdowns in immunity
  • other infectious agents
  • affect TSGs or cell cycle genes
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8
Q

What are the main problems with mammalian regeneration?

A
  • cancer risk (this lecture)
  • lost or altered genetic programme
  • smaller stem cell pool
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9
Q

What is dedifferentiation?

A
  • specialised somatic cells gaining stem cell properties
  • some animals use this for body part regulation (newt, planaria, blastema)
  • in humans, dedifferentiation leads to cancer formation
  • found that tumour cells can be non-specialised cells - acquire stem-cell-like behaviour
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10
Q

How many cancer cells are capable of extensive proliferation ?

A
  • a small subset
  • in liquid tumours, very few isolated cells can form their own colonies
  • in solid tumours, a large number of cells and cell types are required to grow tumours in xenograft models
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11
Q

What are the basic stages of cancer stem cell evolution?

A
  • de novo mutations cause primary cancer and may cause primary CSCs
  • additional genetic/epigenetic changes due to chemo or disease progression leads to secondary tumours and metastatic CSCs with highly variable properties
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12
Q

Where could cancer stem cells come from?

A
  • transformation in normal SCs
  • dedifferentiation
  • either way many mutations required
  • progeny of CSCs arent normal cells but are less proliferative than CSCs like normal progenitors are to normal SCs
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13
Q

What are the sources of heterogeneity in cancer?

A
  • genetic/epigenetic changes and clonal evolution
  • environmental effects on cancer cells
  • cancer stem cell model
  • in aggressive tumours -> a combination of all of these where mutated cells become CSCs - more heterogeneity
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14
Q

What differences in division are associated with cancer stem cells in early stage tumours?

A
  • normally want asymmetrical division 1 stem 1 differentiated
  • early cancer mutations can disrupt the ratio for example downregulation of miR-34a in breast cancer can stop its ability to inhibit proteins involved in stemness and tumorigenesis such as Nanog
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15
Q

How do CSCs affect the tumour - diagram?

A
  • not mutually exlusive don’t always have these properties
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16
Q

What are haematopoetic stem cell cancers?

A
  • leukaemias from stem cells
  • depending on where the hit is in normal blood cell development changes the leukaemia produced
  • in HSCs or progenitors lead to different leukaemias
17
Q

Give two other examples of cancers that can involve stem cells?

A
  • brain cancer
  • breast cancer
18
Q

What is a cell niche?

A
  • microenvironmental cells that nurture stem cells and maintain tissue homeostasis
  • sequesters cells from stimuli that cause their differentiation, apoptosis and other stimuli that would alter stem cell reserves
  • in cancer the niche may adapt to provide for cancer SCs
19
Q

Name 3 pathways involved in self-renewal that are degulated in cancer stem cells?

A
  • wnt deregulated in colon cancer
  • shh
  • notch
  • can be targeted or act as markers
20
Q

How can cancer cells be de-stemmed to slow/halt progression?

A
  • inducing differentiation (e.g. small molecule drugs or retinoic acid)
  • inhibiting self renewal (e.g. inhibiting STAT3)
21
Q

What kind of mutations give a cancer cell a selective advantage over neighbours?

A
  • increased growth, division, movement
  • decreased cell death
  • need most/all of these to become cancer cells
22
Q

How long do different cell types last?

A

same as regen med - intestine, blood, brain, stem cell contribution and cancer risk. somatic cells undergo a limited number of divisions before dying and are being constantly renewed