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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
Q

Describe the markers expressed by haematopoetic stem cells

A

CD34+ CD38-

26
Q

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

A

Rescure of the haematopetic system

27
Q

Describe the marker changes which accompany a leukemogenic event

A

CD34- CD38-

28
Q

If you transplant a CD34- CD38- cells into an immuno compromised mouse what happensn

A

Leukaemia

29
Q

Giloblastoma

A

Most lethal and prevalent form of primary brain tumour

30
Q

What are the two treatments for GBM

A

Surgical resection

Chemo in combination with radiotherapy

31
Q

What property do GBMs exhibit linking them to the cancer stem cell model

A

Heterogeneity

32
Q

Describe the process for capturing neural stem cells in vitro

A

Dissociate the cell

Plate on laminin in presence of FGF2 and EGF

33
Q

What markers do neural stem cells express

A

RC2

34
Q

Gene expressed by glia

A

GFAP

35
Q

Gene expressed by neurones

A

TUJ1

36
Q

What genes are not expressed by neural stem cells

A

GFAP and TUJ1

37
Q

When is a nerual stem cell able to differnetiatie

A

When the permissive envrionment is removed - FGF2 and EGF taken away

38
Q

What is expressed y neural precurrsors

A

DCX

39
Q

What markers similar to RC2 are expressed by stem cells

A

Nestin and Sox2

40
Q

What to GBM cells have similar morphology to

A

Foetal neural stem cells

41
Q

What may be one treatment for GBM targetting the cancer stem cells

A

Indatraline
Selectively kills GBM stem cells

But shows limited effect on the foetal stem cells

42
Q

What are the 3 main approaches to study cancer

A

Xenograft models
Cancer cell lines
Genetically modified animals

43
Q

Describe the process of xenograft models

A

Take tumour cells and transplant into a permissive envrionment

44
Q

How may genetically modified animals be used to study cancer

A

Oncogenes/tumour suppressior gene mutations - look at effect

45
Q

Describe the process of invitro modelling of tumourigeneis

A

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
Q

Sites for primary development of neuroblastoma

A

Spinal nerve root (some)

Most common is in the adrenal gland

47
Q

Where does neuroblastoma orginate from

A

Neural crest (responsible for generation of the peripheral neurones)

48
Q

In agressive neuroblastoma there is high level of

A

Transcritpion factor

MYCN

49
Q

Describe the effect of ectopic overexpression of MYCN

A

Formation of neuroblastoma like tumours

50
Q

What is the maker of neural crest cells

A

Sox10

51
Q

How do neural crest cells arise

A

Arise between the surface ectoderm and neural tube

In response to BMP and Wnt signals

52
Q

Describe how you would generate neuroblastoma cells

A

HESCs exposed to Wnt, BMP and MYCN

When implant give rise to tumours

BMS247 Stem Cells (14 decks)

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