BOD L15 Cancer stem cells

Question 1

What is a cancer stem cell?

Answer 1

Stem cells which have acquired oncogenic mutations.

Question 2

What are cancer stem-like cells?

Answer 2

Mature cells that have become cancerious and have reacquired self-renewal properties.

Question 3

What are cancer stem cells responsible for that make them difficult to treat?

Answer 3

They are responsible for chemoresistnace, recurrance and metastasis.

Question 4

What cellular pathways regulare CSCs?

Answer 4

Question 5

How are cancer stem cells resistant to chemotherapy?

Answer 5

Use of:

ATP-binding casstte (ABC) Transporters.

Aldehyde Dehydrogenase (ALDHs).

BCL-2.

DNA Damage Response (DDR)

Question 6

How do ABC transporters convey chemoresistance for CSCs?

Answer 6

Efflux pumps found on CSC surface. Pump out chemotherapeutic drugs out of the cell against their concentration gradient using ATP.

Responsible for drug efflux.

Question 7

How do ALDHs convey chemoresistance for CSCs?

Answer 7

Enzymes involved in detoxifying aldehydes. This inactivates chemotherpautic compounds.

e.g. cyclophosphamide

Converts aldehydes to weak carboxylic acids via oxidation.

Question 8

How does Bcl-2 support CSC survival?

Answer 8

Bcl-2 is a prosurvival, oncogene

Question 9

How are CSCs able to resist DNA-damaging therapies?

Answer 9

By having a strong DDR.

Highly active (phos.) ATM, CHK1 and 2.

Repairs any DNA damage done by chemotherapy.

Question 10

How can cancer stem cells be isolated?

Answer 10

By using their cell surface markers as targets in a cell sorter machine.

Antibody-IF tag treatment and cell sorter is able to isolate fluorescing cells.

Question 11

What process to CSCs undergo to metastasise?

Answer 11

Epithelial to mesenchymal transition (EMT)

Question 12

EMT is a regular developmental process. Give an example of where it normally occurs

Answer 12

During development, by neural ectoderm cells in development of spinal chord.

Question 13

What two pathways for example are deregulated during EMT

Answer 13

TGFbeta and WNT signalling

Question 14

What is EMT?

Answer 14

Transition of a cell to showing epithelial phenotype to mesenchymal.
Involves things such as:

loss of cell-cell contact/junctions, actn-reogranisation and expression of mesenchymal markers.

Question 15

What happens when CSCs reach target ECM

Answer 15

Revert back to epith.

MET.

Question 16

What is the issue with targeting CSC markers for therapy?

Answer 16

Also expressed in normal tissues.

Off-target toxicity.

For e.g. CD133 expressed by a lot of CSCs but also in normal tissue.

Question 17

What three ways can CSCs be targeted by therapy?

Answer 17

Antibody therapy - mAb therapy

Immuntherapy - treat patient T cells to target CSCs

Nanoparticle-based therapy - nanoparticles linked to an inhibitor/drug