CANCER- angiogenesis Flashcards
what does angiogenesis mean?
formation of new blood vessels
what triggers the release of angiogenic factors?
hypoxia
what are the inhibitors of angiogenesis?
extracellular matrix:
thrombospondin-1
angiostatin
endostatin
soluble factors: sVEGF-R IL-10 IL-12 TNF-a
avB3- receptor
whjat are the activators of angiogenesis?
GF: VEGF family FGF family TGF beta PDGF
soluble factors:
IL-6
factor XIII
TNF- a
cell surface receptor avB3
outline the multistep process of sprouting angiogenesis
- tip/stalk cell selection;
- tip cell navigation and
stalk cell proliferation; - branching coordination;
- stalk elongation, tip cell
fusion, and lumen
formation; - perfusion and vessel
maturation.
what happens in the absence of oxygen?
the HIF-a does not bind to the von hippel-lindau protein. HIF goes into the nucleus, binds to the DNA that codes for the gene responsible for angiogenesis
what does VEGF bind to?
it binds to a cell on the vessel and turns it into a tip cell.
by doing this it tells the surrounding cells to become stalk cells and support the tip cell
what is tip cell selection regulated by?
the Notch pathway
what is the Notch pathway?
essential for development and basic functioning of cells
ligand and receptor on two different cells bind
this binding causes the cleavage of the intercellular domain of notch
this can go into the nucleus and binds to the transcription factor RBP-J
when might angiogenesis occur?
embryonic development, wound healing and in the menstrual cycle.
what controls gene regulation?
HIF – Hypoxia-Inducible Transcription Factor
what controls levels of HIF
pVHL – protein Von Hippel-Lindau tumour suppressor gene
what happens in the presence of oxygen in relation to HIF and pVHL?
pVHL adds a hydroxyproline group to HIF and HIF is degraded by a proteasome.
what are the 5 families of VEGF?
VEGF-A/B/C/D and Placental GF (PlGF)
what are the TK receptors?
VEGFR-1/2/3; and co-receptors neuropilin (Nrp1, Nrp2)