Lecture 8

Question 1

What is a cancer initiating cell?

Answer 1

A normal cell type in which, or in whose daughter, cancer develops

Question 2

What is a tumour initiating cell?

Answer 2

A cancer stem cell

Cancer cell which allows cancer to propergate around the body

Question 3

What is the clonal evolutional model?

Answer 3

Cells divide and gain new mutations to become different cells

Question 4

What is the hierarhcial/stem cell model?

Answer 4

Different types of cells in a tumour come from cancer stem cells

Question 5

What was shown by the CFU-S by Bruce and Van der Gaag?

Answer 5

Only a subset of primary cancer tissue was able to proflierate in vivo; proving heterogenity of tumours and introducing the idea of cancer stem cells

Question 6

Who first coined the idea of CSCs?

Answer 6

Hamburger and Salmon, 1977

Question 7

Which hallmarks of cancer apply to CSCs and hence may be good therapeutic targets?

Answer 7

• Evasion of immune system
• Telomerase inhibitors (for some cancers)
• Induction of inflammation
• Ability to induce inavasion
• Ability to induce angiogenesis
• Resistance to cell death mechanisms

Question 8

What are norman Maitlands hallmarks of CSCs?

Answer 8

1. Isloated CSCs can cause tumour growth
2. Isolated CSC are responsible for invasion and spread
3. Isolated CSCs are present in minimal residual disease after convential treatment
4. CSCs can differentiated from a more primitive phenotype to recognisable tumour phenotypes
5. CSCs have a distinct phenotype to other cells in the tumour

Question 9

What type of cell division is seen in stem cells?

Answer 9

Asymmetric cell division - one cell is different and one cell is a new stem cell for self-renewal

Question 10

Why is assymetric division by stem cells important in cancer?

Answer 10

• Mutation is expressed in non-stem cell and may be killed by immune system or apoptosis etc.
• But in stem cell daughter it is hidden but still present
• When this daughter divides with a new muation this may be able to counteract apoptosis for example and allow the initial mutation to be effective
• Hence by hiding a mutation in the stem cell daughter untill the cell has acquired enough mutations to survive as a non-stem cell

Question 11

Mutations in what type of mice cells can cuase cancer?

Answer 11

Normal colon stem cells but not amplifying cells

Barker et al

Question 12

What are common malignaancy markers of CSCs?

Answer 12

• NFkB
• IL6
• DNA Instability
• AMACR
• MMP
• Resistance to radiation - 10X more resistant

Question 13

What is different about proportions of cells in normal and tumour tissue?

Answer 13

In tumour tissue the stem cell poulation is very small in comparison to what is in normal tissue

Question 14

What five common cancer treatments would not work for treating CSCs?

Why?

Answer 14

1. Androgen abalation - CSC are AR^-
2. Radiotherapy - CSC are not rapidly dividing so not affected
3. Chemotherapy - Express drug efflux transporters
4. Gene therapy - Kills differentiated cells
5. Immunotherapy - Kills differentiated cells

Question 15

How does radiotherapy work?

Answer 15

Creates free radicals which cause damage

Question 16

What does a COMET assay show?

Answer 16

DNA Damage

If DNA is damaged then when ran on a gel will leave a tail behind it of pieces of broken DNA. Amount of DNA in the tail = amount of damage

Question 17

What was shown about CSC by COMET assays?

Answer 17

CSC sustain less damage than amplifying or basal cells due radiotherapy or chemotherapy

Question 18

What could be targeted for CSC therapies?

Answer 18

• Stem cell survival
• Stem cell differentiation
• Stem cell colony formation

Question 19

How were cancer stem cell specific targets found?

Answer 19

siRNA knockdown

Question 20

What is being produced by cancer stem cells but not normal stem cells?

Answer 20

IL6

Question 21

How does IL6 inhibition stop cancer?

Answer 21

Causes CSC to differntiated - and these differntiated cells cannot cause cancer alone