Angiogenesis Flashcards
What is the difference between angiogenesis and vasculogenesis?
Angiogenesis is branching from existing vessels
Vasculogenesis is development of new vessels, not from existing
What are the steps that occur when angiogenesis?
- Selection of sprouting endothelial cell, growth factors present and degradation of surrounding ECM
- Sprout outgrowth and guidance, endothelial must detach from neighbors and extend into the ECM
- Sprout fusion and lumen formation, stalk cell proliferation / vacuole formation
- Perfusion and maturation of the vessel
What is the current theory regarding angiogenesis and tumor growth?
Tumor Growth is Dependent on Angiogenesis
What transcription factors are most important for angiogensesis?
When the cell starts to become hypoxic the growth factors can stimulate angiogenesis to help the tumor cells.
HIF-1alpha becomes activated and dimerizes with HIF-1beta, which then translocates to nucleus becoming transcription factor. Additionally, NFkB is activated and contributes to angiogenesis.
Cell then Expresses: VEGF
How is the vasculature different in tumor tissues and normal tissues?
Normal tissues have ordered vessels throughout and linear
Tumor vasculature has choatic vessels randomly throughout the tissue without order.
What is the advantage of choatic vasculature?
The choatic vessels have gaps between them allowing leakage of materials and allows for movement of the cells.
What aspect of solid tumors vasculature make it hard to treat?
The network of capillaries and lymphatics create pressure within the solid tumor preventing drug therapies from penetrating into the core. Also absence of lymphatics.
What is the Rip-Tag Theory?
Normal islet cells can progress to hyperplastic, then they release signals to bone marrow where Macro/Mast Cells release MMP-9, which allows the release of VEGF from the ECM allowing the hyperplastic cells to become angiogenic.
What was VEGF originally understood to do?
Potent permeability factor, 50,000x more potent than histamine.
How does VEGF activate the cells signaling them for angiogenesis?
VEGFR2 Tyrosine Kinase Signaling
- after binding of VEGF causes dimerization and autophosphorylation of tyrosine kinase activating multitude of pathways.
What receptor is responsible for lymphatogenesis?
VEGFR3
What are common inhibitors of angiogenesis?
Primarily most come from the breakdown of ECM, platelet factors, collagen fragments, etc.
How does NOTCH signaling function?
NOTCH is an extracellular receptor used for cell-cell communication. When the extracellular NOTCH binds to a receptor on another cell a portion of it becomes cleaved binding to the other receptor. This protein gets endocytosed into the cell and it works as a transcription factor turning on/off genes of the opposite cell it came from.
When is Notch important in angiogenesis?
Most important when the tips edges of the sprouts from two sites are coming together to form one lumen.
How is anti-angiogenesis therapy easier than targeting the cancer cells?
The endothelial cells undergoing the angiogenesis are genetically stable and more consistent and easy accessibility within vascularture.
