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Cell Proliferation and Survival Mechanisms Underlying Disease > Cancer, stem cells, and cancer stem cells > Flashcards

Cancer, stem cells, and cancer stem cells Flashcards

- Define tissue stem cells - Explain what is meant by the term "cancer stem cell" - Contrast the terms "tissue stem cell" and "cancer stem cell" - Theorise about the relationship of tissue stem cells to cancer cells of origin

1
Q

Define stem cell

A

a cell which can self-renew and differentiate

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2
Q

What does it mean to differentiate a cell

A

to permanently alter the gene expression

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3
Q

What does it mean when a cell is described as being able to self-renew

A

the cell can divide and make a copy of itself with identical properties

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4
Q

Totipotent

A

can make everything

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5
Q

Pluripotent

A

can make all somatic cells

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6
Q

Multipotent

A

can make many different cell types

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7
Q

Bi-/Tri- etc. potent

A

2/3 etc. cell types

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8
Q

Unipotent

A

can only differentiate into one cell type

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9
Q

What is potency

A
  • refers to the ability of a cell to change
  • depends on how many types a stem cell can differentiate into
  • usually restricted with developmental age/tissue restriction
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10
Q

Embryonic stem cells

A
  • cultured in vitro derived from cells of the early embryo
  • pluripotent -> can make all somatic cell types
  • immortal -> indefinitely self-renew
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11
Q

Adult/tissue stem cells (somatic)

A
  • exist in many (most?) tissues
  • normally contribute to the tissue maintenance
  • numbers, properties and functions vary enormously
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12
Q

General characteristics of somatic stem cells (NOT DEFINING CHARACTERISTICS!)

A
  • rare
  • slow cell cycle (divide infrequently)
  • symnmetric or asymmetric cell division
  • unspecialised
  • present in many adult tissues
  • usually respect germ layer boundaries (reports of trans-germ layer potential/multipotency (controversial))
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13
Q

Division of somatic stem cells

A

must divide exactly 50% of the time -> any deviation from this results in problems and imbalance which gets worse with every cell cycle

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14
Q

Stem cell regeneration

A
  • “regeneration” = homeostasis + repair
  • tissues with a natural turnover (blood, skin, etc.)
  • “reserve cells” for injury repair (muscle)
  • differences between organisms
  • lineage restriction
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15
Q

Biology of cancer stem cells

A
  • develop from normal stem cells that gain the ability to proliferate aberrantly and eventually turn malignant
  • grown clonally into tumours
  • have the potential to metastasize
  • share many characteristics with normal stem cells
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16
Q

Stem cells and cancer

A
  • cancers are caused by mutations
  • somatic cells are often short-lived and post-mitotic
  • mutations may accumulate in long-lived, proliferating cells
  • cancer-causing mutations in stem cells or progenitor cells (all lineage of stem cells will carry that mutation)
17
Q

Normal progression of stem cells vs cancerous progression of stem cells

A

Normal:
1) stem cell can self renew and differentiate into progenitor cell
2) progenitor cell can give rise to oligolineage precursors
3) growth into mature cells

Cancer in stem cells:
1) cancerous stem cell gives rise to cancerous progenitor cells
2) cancerous progenitor cells advance to mature cancer cells

Cancer in progenitor cells
1) healthy stem cell can self-renew and differentiate into progenitor cell
2) mutation in progenitor cell, cells become cancerous
3) give rise to mature cancer cells

18
Q

Tomasetti et al, 2015

A
  • hugely controversial
  • take home message was that cancer is due to bad luck
  • calculated number of stem cells in all tissues and the frequency of division to work out total number of divisions in any tissue
  • plot this against lifetime risk of cancer in any tissue -> strong positive correlation
  • therefore, more stem cells = more frequent division = likelihood of cancer increases
    THIS IS NOT THE CASE!!!
  • paper actually states that it is down to luck whether cancer progresses IN THAT PARTICULAR ORGAN and there are numerous risk factors that are prompted in the graph (e.g. smokers)
  • the more stem cell divisions in a tissue, more likely that tissue is prone to cancer. does not mean that stem cells cause cancer. stem cells divide INFREQUENTLY
19
Q

Cancer stem cells

A
  • Stevens and Little (1954)
  • spontaneous testicular teratomas in inbred strains of mice
  • tumours arise relatively frequently in humans
  • tumours are well-differentiated; cell types represent all cell layers (arise from pluripotent cells)
  • in a certain proportion, tumours are malignant
  • cells are able to differentiate into all cell types
  • these cells are stem cells of the tumour
20
Q

Cancer stem cell beginnings

A
  • some tumours of the reproductive organs contain a huge variety of different cell types
  • teratomas / tetratocarcinomas
  • strains of mice spontaneously get them at high frequency
  • embyonal carcinoma cells
  • can be transplanted and give rise to fresh teratocarcinomas
  • single cells!
    (Kleinsmith and Pierce, 1964)
21
Q

Brief history of cancer and stem cells

A
  • papers as far back as 1951 suggest that tumours are maintained by stem cells
  • at the time the momentum was for radical surgery - lack of evidence for efficacy
  • eventually these studies led to a change in the way we consider tumours
22
Q

Cancer stem cell model

A
  • not all cells in a tumour are the same
  • a subset of cells are able to elaborate tumour heterogeneity
  • numbers can vary
  • cancer stem cell is not necessarily a tissue stem cell that got cancer
  • CSC is a cancer cell with stem cell properties (e.g. self-renewal, differentiation capacity)
23
Q

Supporting evidence

A
  • not all tumours are tumourigenic (Southam et al (1966) autotransplanted tumour cells in patients
  • cancers can differentiate: teratocarcinoma cells from chimeras
  • these studies do not prove the model, prospective purification of CSC required
24
Q

CSC in leukaemias

A

Lapidot et al (1994)
- AML cells in SCID mice
- expansion of AML-CFU but poor proliferation in vitro
- suggests a more immature cell present
- sorted cells to identify initiating cells
- only CD34+ CD38- cells could
- markers similar to HSC
- most likely early progenitor cells (CD90-)

25
Q

CSC in solid tumours

A

Al-Hajj et al (2003)
- breast cancers
- CD44+ CD44- / low lineage - cells are tumourgenic in SCID mice
- 100 cells enough
- mouse tumours same heterogeneity as the originals

Cell Proliferation and Survival Mechanisms Underlying Disease (11 decks)

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