Embryonal and Cancer Stem Cells

Question 1

What animals are able to undergo de-differentiation

Answer 1

Salamander and newt

Question 2

What are the explanations for sources of heterogeneity in cancer

Answer 2

1) Genetic/epigenetic clonal expanion
2) Environmental factors/niches
3) CSC Model
4) Combination of all of the aboce

Question 3

What % of leukaemia cells are thought to be able to cause cancer

Answer 3

1-4%

Question 4

What number of cells are able to cause cancer in solid tumorus

Answer 4

through to be as loow as 1 in 5000

Lead to the thought that CSC were relatively rare in solid tumours

Question 5

Where do CSCs come from

Answer 5

1) transformed normal stem cell

2) Dedifferentiation of committed progentior –> now thought potentially more likely

Question 6

What significance is there with miR34a and CSC

Answer 6

miR34a high in early CSC and then decreases with differentiation of the CSC –> hence may be able to target these regulatory pathways to control CSCs

Question 7

What is the signature of breast CSC

Answer 7

CD44+/CD24low

ALSO PORTRAYS A BAD PROGNOSIS

Question 8

What is the signature of AML CSC

Answer 8

CD34+/CD38-

however CD34-/CD34+ have been observed

Question 9

What 3 signalling pathways have been shown to be v important in CSC

Answer 9

Wnt
Notch
Shh

Question 10

What is the signature of brain tumour CSC

Answer 10

CD133+

However non tumorigenic CD133+ cells have been reported]

Question 11

Why are CSC signatures clinically relvevant

Answer 11

Could be a target for therapy

Could be prognostic

Question 12

What has been used to block notch signalling in CSCs

Answer 12

Gamma secretase blocks notch signalling in breast cancers

Question 13

Can epigenetic alterations affect CSCs

Answer 13

Yes those melanoma CSCs that were shown to survive treatment had epigenetic changes

Question 14

What are the regional differences that affect CSC devellopment in medulloblastoma

Answer 14

In the cerebelllum Shh signalling is sufficient to activate

In the dorsal brainstem Wnt signalling is sufficient to activate

Question 15

What temporal differences also affect leukaemia CSC development

Answer 15

Older pateients: FLKT3 mutations can occur

Throguhout life: Ras mutations

Question 16

What is the significant of imatinib in CSC

Answer 16

Imatinib can be used to treat CSC however patients need to remain on imatinib for life may be due to CSC that are imatinib resistant and can persist.

Question 17

Whats the problem with EMT and CSC

Answer 17

If EMT can generate CSC from any non-tumorigenic cells then even if we target therapy to CSCs then potentially any tumour can relpase it. Hence if we do target CSC then you also need to target tumour bulk cells.