Angiogenesis Flashcards
How are integrins involved in angiogenesis?
Upregulated by angiogenic factors
Promote endothelial cell survival during sprouting.
What is the rip tag2 mouse model?
Rat insulin promoter drives expression of large and small SV40 T antigen.
Large t antigen suppresses p53 and Rb
In islets mice develop insulin PNAS.
8-12% hyperplastic islets become angiogenic and 3% –> carcinomas.
How are tumour vessels distinct from normal vessels?
Endothelial cells overlap, bridges, protrusions, tunnels, abnormal cell-cell connections and LEAKY.
What are lymphatics and how are they involved?
Take interstitial fluids from tissues back into circulation.
Vital for IS as have nodes where I responses raised.
Tumours promote lymphatic vessel growth into tumours exploited to METASTASISE.
How is VEGF-a involved in angiogenesis?
Increases proliferation, migration and EC progenitor mobilisation from bone marrow. Reduces EC apoptosis.
Why is directly targeting angiogenesis problematic?
Hypoxia and increased pH –> more aggressive cancer phenotype.
Hypoxia inhibits function of infiltrating immune cells.
Hypoxia promotes chemo and radio t resistance.
Killing vascularise prevents chemo getting to tumour.
What is the angiogenic switch?
Activated by: VEGF-a, b, c, FGF-1,2…
Inhibited by thrombospondin 1,2 interferon a/b, angiostatin, collagen IV fragments.
Time restricted event in which balance between pro and anti angiogenic factors tilts towards pro.
How do we know oxygen can only diffuse so far?
pO2 (1997) - pO2 drops off very quickly at ~100uM
Hlatky et al (2002) - haematoxylin stain a cross section of a tissue.
CD31 - endothelial cell marker (brown stain). Diffuse blue nucleus = viable cell.
Well-perfused tissues reside within 100uM of blood vessel.
