Mechanisms of angiogenesis

Question 1

What is stroma?

Answer 1

all the non-malignant cells within a tumour

Question 2

Are stromal components changed in tumours?

Answer 2

yes, it creates a wound that won’t heal

Question 3

What is the most important stroma cell?

Answer 3

Endothelial cells, forming the lining of all blood vessels

Question 4

Basic angiogenic steps

Answer 4

1. dormant
2. perivascular detachment and vessel dilation
3. onset of angiogenic sprouting
4. continuous sprouting; new vessel formation and maturation; recruitment of perivascular cells
5. tumour vasculature

Question 5

Vasculogenesis vs angiogenesis

Answer 5

vasculogenesis is initial blood vessel development by de novo generation of ECs whereas angiogenesis is growth of new vessels from existing vasculature

Question 6

When does vasculogenesis occur?

Answer 6

in enbryogenesis

Question 7

Can tumours grow without angiogenesis?

Answer 7

yes, they can grow along existing blood vessels (vessel co-option) common in gliomas and following anti-angiogenic therapy

Question 8

What are tip cells?

Answer 8

at the end of a growing sprout, filopodia rich, not perfused and highly motile EC cells

Question 9

What are stalk cells?

Answer 9

Highly proliferative EC cells that form the lumen. BrdU stain can identify them

Question 10

faulty assumptions in angiogenic staining

Answer 10

1. assumes you can correctly detect a protein
2. creates a faulty binary view of samples

Question 11

What has caused flaws in angiogenic therapy research?

Answer 11

research has focused solely on the tip cells, only about 5% of ECs

Question 12

Do angiogenic cells effect surrounding cells?

Answer 12

yes, they remodel the tissue around them, particularly basement membrane and ECM

Question 13

Immune interraction?

Answer 13

Angiogenic ECs are highly immunogenic meaning they interact with immune cells

Question 14

Tip stalk cell formation

Answer 14

1. selection of sprouting ECs
2. sprout outgrowth and guidance
3. sprout fusion and lumen formation
4. perfusion and maturation

Question 15

Angiogenesis regulators

Answer 15

hypoxia, VEGF, endothelial cell metabolic state, angiopoietins and PDGF

Question 16

How does VEGF work?

Answer 16

VEGF (vascular endothelial growth factor) is secreted by HIF expressing cells, strongly induced by hypoxia
exists as many different isoforms with different genes
diverse action (fat, neuronal and myeloid)

Question 17

Differing effects of VEGF isoforms

Answer 17

different ability to interact with ECM components
alters diffusibility through the ECM
impacts on ability to activate receptors
impacts on receptor clustering
impacts angiogenesis

Question 18

different VEGF angiogenic phenotypes

Answer 18

traditional RTK signalling vs AKT dependent and modulation of quiescence

Question 19

basic initiation of vessel formation

Answer 19

1. activation
2. selection
3. sprouting
4. elongation