Angiogenesis & Stroma

Question 1

How do neoplastic stromal cells communicate?

Answer 1

Heterotypical interactions:
Mitogenic growth factors
Growth inhibitors
Trophic factors

Question 2

How do tumours heal?

Answer 2

Tumours do not heal, leaky blood vessels.

Fibrinogen contacts cancer cells and form fibrin cells in tumours

Question 3

What do stroma release as a wound response?

Answer 3

Stroma release PDGF and TGF-β

Question 4

What causes tumour tissue to be stiffer than normal tissue?

Answer 4

Excessive ECM and myofibrioblast contractions

Involvement of carcinoma-associated fibroblasts

Question 5

Describe the process of angiogenesis

Answer 5

Endothelial cells release PDGF and heparin binding EGF that attracts pericytes and smooth muscle cells.
Pericytes then release VEGF & angiopoietin-1 giving survival and angiogenic signals to edothelial cells.

Question 6

Why is tumour vasculature leaky and chaotic?

Answer 6

Dysregulation of VEGF

Question 7

What are the advantages of anti-angiogenic therapies?

Answer 7

Many pathways to block angiogenesis
Targets health endothelial cells that are genetically normal with minimal genetic instability compared to tumour cells that can gain resistance

Question 8

What is vasculogenic mimicry?

Answer 8

Alternate strategy used by tumours against anti-angiogenic therapies
Involves to formation of microvascular channels by neoplastic cells, independent of endothelial cells