Chapter 10
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What is angiogenesis?
It is the process of forming new blood vessels from pre-existing ones by the growth of and migration of endothelial cells.
What is the process of forming new vessels from pre-existing ones?
Sprouting
When is angiogenesis normally seen? (3 things)
• embryogenesis • Wound healing • Female reproductive cycle
What is the diffusion limit of oxygen? What does this mean?
100-200 micrometers all cells must be within this range in order to receive the essential oxygen and nutrients
What typically happens to the cells within the core of the tumor?
They die of necrosis
To sprout from pre-existing vessels requires major reorganization. What must occur?
• Destabilization of the current vessels • Proliferation and migration of the endothelial cells • Maturation
What regulates this?
The interaction between soluble mediators and their receptor.
Where do the mediators come from?
They are secreted by tumor cells and stromal cells.
True or false: the vasculature after new vessels formed during tumor growth is similar to vessels formed after wound healing.
False. it will be leaky and tortuous
What is the angiogenic switch?
It is the balance between the inducers and inhibitors that activate or inactive angiogenesis.
How may angiogenesis be turned “on”?
• By increasing the activity of inducers • Decreasing the activity of inhibitors
What are some of the anti-angiogenic factors we talked about?
• Angiostatin • Endostatin • Prolactin • Protein 53 • Thrombospondin
What are some of the pro-angiogenic factors we talked about?
• VEGF • fibroblast growth factor • hepatocyte growth factor • EGF • PDGF
What are the non-specific growth factors that are important for angiogenesis?
• EGF • FGF • HGF • PDGF
What are the vascular endothelium specific growth factors?
• VEGF - important for initiation of angiogenesis • Angiopoietins (bind to Tie receptors) and are important for maturation • Ephrins (bind to ephrin receptors) important for maturation as well
What are the five members of the VEGF family?
VEGF a, b, c, d, and Placental Growth Factor
What are the three VEGF receptors? What type of protein are they?
VEGF - 1, 2, 3 They are kinases
What interaction of VEGF and its receptor is responsible for the majority of angiogenesis?
VEGF A with VEGFR 2
What are the characteristics of VEGFR1?
it has weak affinity and kind of acts like a decoy.
What does VEGF C interact with and do?
It interacts with VEGFR 3 and contributes to the development of lymphatic vessels.
What secretes VEGF?
Tumor cells and the tumor-infiltrating immune cells do this
What releases sequestered VEGF in the ECM?
MMPs
What is VEGF important for? ( three things)
• endothelial cell proliferation • Inducing permeability and leakage, by destabilizing the mature vessel allowing for sprouting
What are the VEGF responsive genes?
• EGF (epiregulin) • MMPs