Tumour Microenvironment and Inducing Angiogenesis Flashcards
Summary of Tumour microenvironment and Inducing angiogenesis
Tumour can grow exponentially die to forming a blood vessel network
What are cancer stem cells?
Responsible for making new tumour cells
Enhanced resistance to drugs
How can we target cancer stem cells?
They express specific markers (eg:CD24)
By enzymes (ALDH)
By transcription factors
Activated signalling pathways
Normoxia in tumour cells
Well- oxygenated region
Hypoxia in tumour cells
Poorly oxygenated regions
Cells dormant
Less susceptible to chemo
What cancer cells present HIF1-alpha
Hypoxic cancer cells due to altered angiogenesis
How does Pimonidazole work
Binds to thiol containing proteins in hypoxic cells
What does lack of oxygen do to cancer cells?
Necrosis- cell contents spilled causing inflammation and injury to nearby cells
Neoangiogenesis
Cancer cells need oxygen, nutrients and removal of waste
Promotes new blood vessels
Angiogenic switch
Tumour secretes angiogenic factors which stimulates angiogenesis
Cases rapid growth
Neovascularization
Facilitates metastasis as new vessels grow, allows rapid tumour growth
How is angiogenesis induced?
tumour releases proangiogenic factors to endothelial cells (VEGF, FGF, PDGF)
Hypoxia oncogenes
VHL, HIF1-alpha
How do tumours induce angiogenesis?
MMPS are secreted
which digest extracellular matrix
MMPs allow vessels to grow towards tumour
VEGF and FGF and VDGF are secreted by tumour to cause blood vessels to grow in gap
sprouting endothelial cells express integrin