1. Why Is Angiogenesis Needed Flashcards
What is the role of the blood?
Provides oxygen and nutrients
Removes (metabolic) waste products eg metabolic acid
What is VEGF
Vascular endothelium growth factor.
It induces angiogenesis
Which cancers can bevacizumab be used to treat?
Cancers of the:
- Colorectal
- Lung
- Kidney
- Brain
What does CB31 stain?
Blood vessels (endothelium)
What does bevacizumab do?
Reduces tumour vascularisation
Describe the outcome of tumour vascularization of samples treated with and without bevacizumab
Tumours continue to grow in both samples.
There is more necrosis in ample treated with bevacizumab due to targeting VEGF, decreasing vascularization.
Briefly explain what happens in a tissue leading up to tumour angiogenesis
- Tumour cells grow along pre-existing blood vessels
- Increased tumour growth leads to hypoxia and necrosis. The tumour outgrows the blood supply.
- Angiogenic sprouting is initiated. Hypoxia induces the expression of kinochines which induce angiogenesis
What is the diffusion distance of oxygen in tumour tissue?
80-100 um
How do tumour cells contribute to hypoxia in the tissues it invades?
- The tumour cells have high metabolic
- Uncontrolled growth of tumour cells
At what distance from blood vessels is necrosis observed in tumour cells
> 180um (O2 has diffusion distance of 80-100um)
Which markers are used to observe:
A) hypoxia
B) blood vessels
A) EF5
B) PECAM/CP31
What is HIF
Hypoxia inducible factors
What does low levels of O2 lead to? (Proteins in angiogenesis)
Stabilization of HIF1a and HIF2a
Briefly describe how HIFs behave in hypoxic conditions
- HIF1a and HIF2a are stabilized, under normal conditions they are constantly degraded.
- They regulate the expression of pro-angiogenic proteins
- When stabilized, they heterodimerise with HIF1/2B (ARNT)
- They bind to HRE (HIF response element) sequence in DNA, to then regulate genes involved in many aspects of hallmarks of cancer (proliferation, metabolis, metastasis, angiogenesis, etc)
Describe 3 proteins and their processes which are increased in response to angiogenesis
- VEGF - production leads to auto rinse signals for angiogenesis
- MMPs - frees pro-angiogenic factors from the stroma
- Angiopoietin-2 - increases vascular basement membrane degradation & endothelial cell migration