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BMS247 Stem Cells > L9 - Cancer Stem Cells > Flashcards

L9 - Cancer Stem Cells Flashcards

1
Q

Pluripotent

A

Generate all of the cell types including the germ cells

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2
Q

Multipotent

A

Genergate numerous cells types but there is more restriction seen here

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3
Q

Niche

A

Specialised microenvironment which keeps stem cells self-renewing

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4
Q

What happens when SCs leave the niche

A

Exposed to pro-differentiation signals and are then fated to become more specialised cell types

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5
Q

Oncogene def

A

Gene capable of transforming a normal cell into a tumour cell

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6
Q

Tumour supressor gene

A

Genes which restrict proliferation through cell cycle arrest and apoptosis

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7
Q

Chemical affects

A

Smoking

B-naphthylamine

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8
Q

Parasitic effects

A

Schistosoma

Clonorchis

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9
Q

Radiation

A

UV

Ionising

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10
Q

What viruses can give rise to cancer

A

HPV/EBV/HBV

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11
Q

What does the heterogenetiy of tumours mean

A

The idea that cells within the same tumour often exhibit differences

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12
Q

Cells of the same the same tumour may exhibit differences in terms of

A 
Dif state 
Prolif rate 
Migratory and invasive 
Size 
Therapeutic resposne
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13
Q

What is intra-tumour heterogenetity

A

Differences within cells of the same tumour

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14
Q

Difference between different tumours

A

Inter-tumour heterogeneity

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15
Q

Describe the stochastic model of cancer

A

All cells are tumour initiating
All have the same potency
All able to either self renew or differentiate

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16
Q

Describe the cancer stem cell model

A

Only a small subet of tumour cells have the ability for long term self renewal
These cells give ise to comitted progenitors that eventually terminally differentiate

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17
Q

Describe the cell cyclee of cancer stem cells

A

Slow cycle and some even lie dormant

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18
Q

Are cancer cells suspeptible to drugs

A

No drugs target proliferating cells so CSCs are effectively drug reisstant

Cancer stem cells which are not killed then able to reseed the tumour

Tumour grows back with heterogenetiy

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19
Q

Desribe the role of SELF RENEWAL in cancer stem cells and normal stem cells

A

Homeostasis in normal

Tumour growth

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20
Q

Desribe the role of Differentiation in cancer stem cells and normal stem cells

A

Maintenance of organ functionality with ability for functional reconstrucution

Tumour heterogenetiy - selection advantage also has thee ability to initiate a tumour

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21
Q

Describe the mechanism of cancer stem cell formation (2)

A

Reprogramming event to cancer stem cell like entity

Oncogenic transformation of pre existing stem cells

22
Q

what is the invitro potential of capturing cancer stem cells

A

Establishment of cell lines which can self-renew and differentiate

23
Q

What is the in vivo potential of captured cancer stem cells

A

Have the ability to give rise to cancer following transplantation into animals

24
Q

AML

A

Actute myeloid leukameia

25
Describe the markers expressed by haematopoetic stem cells
CD34+ CD38-
26
In an immuno compromised mouse sublethal radition exposure leads to no haem system forming What happens if you transplant a WT HSC into that mouse
Rescure of the haematopetic system
27
Describe the marker changes which accompany a leukemogenic event
CD34- CD38-
28
If you transplant a CD34- CD38- cells into an immuno compromised mouse what happensn
Leukaemia
29
Giloblastoma
Most lethal and prevalent form of primary brain tumour
30
What are the two treatments for GBM
Surgical resection | Chemo in combination with radiotherapy
31
What property do GBMs exhibit linking them to the cancer stem cell model
Heterogeneity
32
Describe the process for capturing neural stem cells in vitro
Dissociate the cell | Plate on laminin in presence of FGF2 and EGF
33
What markers do neural stem cells express
RC2
34
Gene expressed by glia
GFAP
35
Gene expressed by neurones
TUJ1
36
What genes are not expressed by neural stem cells
GFAP and TUJ1
37
When is a nerual stem cell able to differnetiatie
When the permissive envrionment is removed - FGF2 and EGF taken away
38
What is expressed y neural precurrsors
DCX
39
What markers similar to RC2 are expressed by stem cells
Nestin and Sox2
40
What to GBM cells have similar morphology to
Foetal neural stem cells
41
What may be one treatment for GBM targetting the cancer stem cells
Indatraline Selectively kills GBM stem cells But shows limited effect on the foetal stem cells
42
What are the 3 main approaches to study cancer
Xenograft models Cancer cell lines Genetically modified animals
43
Describe the process of xenograft models
Take tumour cells and transplant into a permissive envrionment
44
How may genetically modified animals be used to study cancer
Oncogenes/tumour suppressior gene mutations - look at effect
45
Describe the process of invitro modelling of tumourigeneis
Take hESC and introdce oncogenic mutation Take est cancer steml lines and reprogram to ips stage Invitro dif to cell type of interest View phenotype
46
Sites for primary development of neuroblastoma
Spinal nerve root (some) Most common is in the adrenal gland
47
Where does neuroblastoma orginate from
Neural crest (responsible for generation of the peripheral neurones)
48
In agressive neuroblastoma there is high level of
Transcritpion factor MYCN
49
Describe the effect of ectopic overexpression of MYCN
Formation of neuroblastoma like tumours
50
What is the maker of neural crest cells
Sox10
51
How do neural crest cells arise
Arise between the surface ectoderm and neural tube In response to BMP and Wnt signals
52
Describe how you would generate neuroblastoma cells
HESCs exposed to Wnt, BMP and MYCN | When implant give rise to tumours

BMS247 Stem Cells (14 decks)

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