Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BMS247 - Stem cells > Cancer and stem cells > Flashcards

Cancer and stem cells Flashcards

1
Q

Where are all the precursors of the cell types of the body?

A

In the 3 germ layers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

When do the pluripotent cells start differentiating?

A

During gastrulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What happens to the stem cells when they leave the niche?

A

They begin to differentiate and give rise to more specialised cell types

Under the influence of pro-differentiation signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What development does the cell cycle drive?

A

BOTH embryonic and postnatal development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What genes disrupt the cell cycle?

A
  • Oncogenes: capable of transforming a normal cell –> cancer cell when ACTIVE
  • TSG: restrict proliferation when active (mutations inactivate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are carcinogenic factors?

A

1) Chemical:
- Smoking

2) Parasites

3) Radiation:
- UV
- Ionising

4) Viruses:
- HPV
- HBV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are carcinogenic factors capable of?

A

Activating oncogenes

Inhibiting TSGs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the appearance of tumours

What does this mean?

A

Heterogeneous

Cells in the SAME tumour exhibit DIFFERENCES in terms of:

  • Differentiation rate
  • Proliferation rate
  • Migratory and invasive capacity
  • Size
  • Therapeutic response
  • Tumourgenicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is ‘intra-tumour heterogeneity’

A

Differences between cells in the same tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is ‘inter-tumour heterogeneity’?

A

Differences between DIFFERENT tumours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is the heterogeneity between tumours explained?

A

2 different models:
1) Stochastic

2) Cancer stem cell model

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the stochastic model for cancer?

A

States that ALL tumour cells are EQUIPOTENT and can either differentiate or self-renew

Cells have unlimited proliferative capacity

ALL the cells of a tumour are tumour-initiating

All tumour cells are EQUALLY SUSCEPTIBLE to treatment (all have the same proliferative potential, all can be targeted by anti-proliferative drugs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does equipotent mean?

A

Equal capacity to differentiate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the problems with the stochastic model for cancer?

A

Tumours tend to RECUR after treatment, indicating:

  • Not all cells are EQUALLY vulnerable to anti-proliferative treatments (some are differentially resistant to the drugs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the cancer stem cell model for cancer?

A

States that only a SUBSET of tumour cells have the ability for long-term self renewal and therefore cancer formation

These cells give rise to COMMITTED progenitors with LIMITED proliferative potential that will eventually terminally differentiate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does the cancer stem cell model form?

A

A hierarchy of differentiation:

  • Tumour stays heterogenous
  • Small reservoir os slowly proliferating CSCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the therapeutic implications of the cancer stem cell model of cancer?

A

1) CSCs represent a very SMALL fraction of the cells in the tumour
2) If treat the cancer with drug that kills mainly proliferating cells - CSCs ESCAPE treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why do CSCs escape the drug treatment that kills mainly proliferating cells?

A

CSCs are slowly proliferating/dormant

Resistant to the treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How can normal stem cells be functionally tested?

A

Ability for functional reconstruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How can cancer stem cells be functionally tested?

A

Ability to initiate a tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the difference between the need for self-renewal in normal stem cells and cancer stem cells?

A

Normal - needed in order to maintain HOMEOSTASIS

Cancer - serves as a tool for TUMOUR GROWTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the difference/similarities between the regulation of normal stem cells and cancer stem cells?

A

Similarities: Same signalling pathways (eg. Wnt)

Differences: Cancer - ELEVATED signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the different possibilities for a cancer cell to arise?

A

1) REPROGRAMMING event:
- One or more genetic/epigenetic transformation events that drive specialised cells (differentiated from stem cells) BACK into cancer stem cell entity
- Gives the cells capacity for self-renewal and differentiation
2) ONCOGENIC transformation:
- Normal stem cell transformed into a CSC that fuels tumour growth
- Through number of genetic/epigenetic transformations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Are the 2 mechanisms that can cause cancer mutually exclusive?

A

NO - they can happen in the SAME tumour

BUT, different cancers can be driven by one more than the other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What 2 features allow cancer stem cells to be characterised?

A

1) In VITRO potential (Establish cell lines that can self-renew and differentiate)
2) In VIVO potential (Ability to give rise to cancer following transplantation into animals)

26
Q

What is acute myeloid leukaemia?

A

Blood cancer affecting the myeloid lineage

27
Q

What do haemopotetic stem cells give rise to?

A

ALL blood cells

28
Q

Where is the niche for haemopotetic stem cells?

A

In the bone marrow

29
Q

How are haemopotetic stem cells characterised?

A

By the POSITIVE expression of CD34

By the NEGATIVE expression of CD38

30
Q

What assay for testing HSCs ability?

A
  • Take mice lacking the immune system and sub-lethally radiate the mouse to wipe of the HPC system
  • -> eventually the mice DIE

BUT
- If transplant a SINGLE HSC into the mouse - can rescue the ENTIRE haematopoietic system

31
Q

What happens to the Haemopoietic cell in leukemia?

A
  • Undergoes ONE or MORE transformation events under the influence of genetic drivers

–> TRANSFORMED into a leukemic stem cell that has the ability to self-renew and differentiate
(With a biast differentiation to the myeloid lineage)

32
Q

What happens if transplant a leukemic stem cell into an immunocompromised mouse with no HP system?

A

Generate BLOOD CANCERS in the mouse

33
Q

What is glioblastoma?

A

An aggressive and invasive BRAIN CANCER

34
Q

What is the treatment for glioblastoma?

A
  • Surgical resection
  • Radition
  • Chemotherapy
35
Q

As glioblastomas are heterogenous, what idea did this bring forward?

A

That they are driven by stem cells (cancer stem cell model)

In the stochastic model - all the cells are EQUAL (not driven by CSCs)

36
Q

How can multi potent stem cells be captured in vitro?

A
  • Dissociate the cells from a brain

- Plate the cells of laminin in the presence of cytokines: FGF2 and EGF

37
Q

What are the undifferentiated markers for NS cells?

What are these cells negative for?

A

RC2

Negative for differentiation markers: GFAP (glia) and TUJ1 (neurons)

38
Q

Can we isolate glioblastoma stem cells using the same methods as isolating NSCs?

Why?

A

Yes

As glioblastoma is driven by NS cells - NS cells are transformed into CSCs

39
Q

Describe the glioblastoma stem cells are isolated

What does this produce?

A

Dissociate the cells from the glioblastoma and CULTURE them under the SAME conditions as the NSCs
(On laminin, in the presence of cytokines)

Produces self-renewing GBM colonies that express undifferentiated markers - Indicating the self-renewal stage

40
Q

What are the undifferentiated markers of GBM colonies?

A

Nestin/Sox2

41
Q

What happens if remove the self-renewal factors from the GBM colonies?

A

Forces the GBM stem cells to DIFFERENTIATE

42
Q

What do the GBM glial cells express?

A

GFAP

43
Q

What do the GBM neural precursors express?

A

Dcx

44
Q

What is the difference between GBM cells and normal NSCs?

A

DIFFERENT tumours give rise to DIFFERENT GBM stem cell lines with DIFFERENT capacities for differentiation

45
Q

What does the injection of undifferentiated GBM stem cells into the brain of mice cause?

A

GBM-like tumour

46
Q

What can in vitro cancer cell systems be used for?

Example?

A

Drug screens - to identify suitable drugs to treat the tumours:
- Identify molecules that create/block a certain phenotype

Example:
- GBM and normal foetal NS cells - look similar when untreated

  • Treat with INDATRALINE: selectively kills the GB cells through growth arrest, with a less severe effect on the NS cells
47
Q

What are the 3 main approaches to study cancer?

A

1) Xenograft models - Inject tumour cells into a permissive environment (eg. kidney)
2) Cancer cell lines in the petri dish - form tumours
3) Genetically modified animals - Manipulated to over express oncogenes or TSG mutations

48
Q

What are the limitations of using cell lines and animal models to study cancer?

What can be a solution to these problems?

A
  • Failure to capture the TRANSITION from a normal to a tumourgenic phenotype in:
    A traceable manner
    In human context
  • Lack of mechanistic insight (mechanism that drives the process)

Solution:
- iPS cells

49
Q

How can iPS be used to study cancer?

A

1) iPS from patients that carry the tumour
- iPS represents the early emrbyonic stem cells of these patients
2) Can introduce oncogenic mutation into the human pluripotent stem cell

These cells differentiate into the cell origin of the tumour:
- Can examine the phenotype and look for the hallmarks of cancer

50
Q

What are the hallmarks of cancer?

A
  • Sustained proliferation
  • Impaired differentiation
  • Formation of a cancer if transplant into a permissive environment
51
Q

What is neuroblastoma?

A

Common solid tumour in infants/young children

Above the kidney, in the adrenal gland
Or
Around the spinal cord

52
Q

Where does neuroblastoma originate from?

A

The neural crest

53
Q

What do aggressive neuroblastomas express?

What is this?

A

High levels of the transcription factor MYCN

An oncogene

54
Q

What does ectopic expression of MYCN in normal neural crest cells in the mouse cause?

A

Neuroblastoma-like tumours

55
Q

Where do the neural crest cells come from?

A

The ECTODERM

56
Q

What is the main marker of neural crest cells?

A

Sox10

57
Q

How can the production of neural crest cells be mimicked using iPS cells in vitro?

Why do we want to do this?

A

Capture iPS cells in conditions that promote neural crest emergence in the neural tube (Wnt, BMP)

Want to do this in order to study neuroblastoma:
- Want to see what happens during the transformation from a neural crest into a neuroblast

  • BUT, this can’t be seen in vitro
  • May be able to instead, differentiate iPS cells –> neural crest and over express MYCN to get the neuroblastoma phenotype
58
Q

What does the capture of iPS cells in conditions that promote neural crest emergence in the neural tube (Wnt, BMP) generate?

What happens if over express MYCN in these cells?

A

Cells that represent the neural crest and express Sox10

If over express MYCN:
- Higher colonic efficiency

  • Differentiate faster compared to control
  • If graft into a mouse –> form a tumour that represents human neuroblastoma
59
Q

What method could be used to found the mechanism from the neural crest to transformed neuroblastoma cells?

A
  • Differentiate iPS cells –> neural crest

- Over express MYCN –> get the neuroblastoma phenotype

60
Q

What is ‘colonic efficiency’?

A

If take cells and re plate them - give rise to more colonies

BMS247 - Stem cells (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions