3 Tumour Biology

Question 1

What is metastasis?

Answer 1

tumour deposit discontinuous with the primary tumour

Question 2

What are the 4 key properties of metastatic cell?

Answer 2

detachment from primary mass

Invasion of ECM

Adhesion to endothelium and extravasation

Colonisation of and survival in secondary organ

Question 3

What happens to adhesion molecules to allow a cell to detach from the primary mass?

Answer 3

they are downregulated

Question 4

Which adhesion molecule is most commonly downregulated?

Answer 4

E-cadherin

Question 5

What normally happens to free B-catenin?

Answer 5

removed by a protein complex via proteasome mediated degradation

Question 6

Why might loss of APC promote free B-catenin functio?

Answer 6

renders the B-catenin degradation complex non-functional

Question 7

What does free B-catenin do?

Answer 7

binds to Lef/TCF transcription factors

initiates transcription of oncogenes

Question 8

What oncogene might B-catenin induce the transcipriton of?

What does this cause?

Answer 8

MYC

uncontrolled proliferation

Question 9

What sort of degrading enzymes are common in tissue invasion?

Answer 9

Matric Metalloproetinases (MMPs)

Question 10

What are MMPs secreted by?

Answer 10

tumour cells

stromal cells

Question 11

What are stromal cells?

Answer 11

non-malignant cells surorunding the malignant tumour cells

these are still part of the tumour

Question 12

What causes the stomal cells underlying the basement membrane to produce degrading enzymes?

Answer 12

pre-malignancy

epithelium release soluble factors activating the stroma underlying the BM

Question 13

What 2 key processes facilitate tissue invasion?

Answer 13

degrading enzymes

cell movement

Question 14

What facilitates cancer cell movement?

Answer 14

EMT - epithelial mesenchyme transition

Question 15

What process in wound healing is key to producing new epithelial cells?

Answer 15

MET - mesenchyme epithelial transition

Question 16

What do tumour cells doe as they reach their secondary site?

Answer 16

slow (size restriction)

adhere (receptor ligand interactions)

Question 17

Why is cancer spread no random?

Answer 17

physical location of secondary site relative to primary site

better match for secondary sites for individual cancer types

Question 18

What is the basis of the seed and soil hypothesis?

Answer 18

nature of environment and growth factor mix

Question 19

How do tumours establish a metastatic niche?

Answer 19

secrete soluble factors

Question 20

Why is establishing a metaststic niche so important?

Answer 20

modifies the surrounding site

prepares for later colonisation

Question 21

What are the 2 key responses to hypoxia i tumour cells?

Answer 21

angiogenesis

anaerobic respiration

Question 22

What are the responses to hypoxia stimulated by?

Answer 22

hypoxia inducible transcription factors

Question 23

What stimulates angiogenesis?

Answer 23

VEGF - vascular endothelial growth factor

Question 24

What is the morphology of blood vessels produces in angiogenesis?

Why?

Answer 24

chaotic and leaky endothelium

facilitates further metastsasis

Question 25

How can tumour cells enhance glycolysis?

Answer 25

increased glucose uptake

increase glucose metabolism

Question 26

Give one example of an enzyme upregulated as a response to hypoxia?

Answer 26

hexokinase

Question 27

What imaging process takes advantage of tumour cell glycolysis?

Answer 27

PET using glucose analogue flourodeoxyglucose (FdG)

Question 28

How does glycolysis inhibit surrounding healthy cell growth?

What is the effect of this?

Answer 28

outcompeting healthy cells for scarce glucose supply
creates an acidic environment

kills surrounding cells, allowing the tumour to invade local environment