42. Angiogenesis and Metastasis

Question 1

What is metastasis?

Answer 1

Spread of tumour cells from primary site

Question 2

How do tumours spread in metastasis?

Answer 2

Via blood
lymph
within body cavities

Question 3

Where do breast metastases go?

Answer 3

Bone

Brain

Question 4

Where do prostate metastases go?

Answer 4

Bone

Question 5

Where do stomach metastases go?

Answer 5

Liver

Ovary

Question 6

Where do colon metastases go?

Answer 6

Liver

Lungs

Question 7

Where do melanoma metastases go?

Answer 7

Brain
Liver
Bowel

Question 8

What is the seed and soil theory?

Answer 8

Cells disperse at random but only grow in organs with correct factors for growth

Question 9

What is the mechanistic theory?

Answer 9

First site is the closest one in which there are small blood vessels

Question 10

What are the steps of metastasis?

Answer 10

1. Disruption of cell interactions, disruption of membrane
2. Invasion and migration through membrane
3. Intravasion into blood/lymph vessel
4. Survival in circulation
5. Extravasion out of vessel and migration into new tissue
6. Survival in new tissue
7. Angiogenesis

Question 11

What are the 3 steps in invasion?

Answer 11

1. Attachment (cell adhesion molecules)
2. Proteolysis (enzymes)
3. Migration (motility factors)

Question 12

What is angiogenesis?

Answer 12

New blood vessels form from pre-existing vasculature

Question 13

What is vasculogenesis?

Answer 13

New vessel synthesis from endothelial progenitor cells

Question 14

What are the steps in angiogenesis?

Answer 14

1. Secretion of angiogenic factors by tumour cells (VEGF)
2. Release of proteases from endothelial cells
3. Permeabilisation of blood vessel wall and release of vascular endothelial cells
4. Migration of endothelial cells into interstitial space and tumour
5. Endothelial cell proliferation
6. Lumen formatin
7. Fusion of newly formed vessels
8. Initiation of blood flow

Question 15

What are the factors that stimulate angiogenesis?

Answer 15

Cytokines and growth factors (VEGF, EGF, PDGF)
Hypoxia
Oncogene activation
Loss of tumour suppressor genes

Question 16

What are the effects of hypoxia on a tumour?

Answer 16

Stimulates angiogenesis
Impairs drug delivery
Selects for more aggressive cells
Resistant to chemo as not proliferating

Question 17

Name 5 angiogenesis inhibitors

Answer 17

Angiostatin
Endostatin
Interferons
Platelet factor 4
TIMPs

Question 18

What are the features of tumour associated blood vessels?

Answer 18

Leaky
Irregular branching
Abnormal shunts
Less sensitive to chemo
Poor drug delivery