Lecture notes
First Class Lecture notes Cancer Biology (DNA and Disease)
- Module
- Cancer Biology
- Institution
- University Of Bath (UoB)
Angiogenesis lecture notes
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ANGIOGENESISTHE
ANGIOGENIC SWITCH IS NEESSARY FOR TUMOUR GROWTH AND
METASTASIS:
Angiogenesis = growth of new vasculature/ blood vessels
Steps in network formation
and maturation during
embryonic (physiological)
angiogenesis (a) and
tumour (pathological)
angiogenesis (b).
(b) ECs and mural cells
derived from circulating
precursor cells or from the
host vasculature form
networks that are structurally and functionally abnormal.
Continual remodelling by inappropriate patterns of growth and
regression (cell apoptosis and necrosis) contribute to the
instability of these networks.
Endothelial cells that line blood vessels in tumour do not divide,
so before the angiogenic switch is triggered, tumours never
grow larger than a pea because the vasculature cannot keep
up. This switch triggering angiogenesis determines whether a
, full blown tumour develops. Tumour cells secrete angiogenic
proteins because of mutations, which enable endothelial cells
to divide, allowing the tumour to receive oxygen and nutrients
and undergo an explosive proliferation.
Vascular networks in tumours:
In normal angiogenesis, certain progenitor cells enable the
growth of new vascular networks – these networks are very
rigid and structured.
Tumour vasculature however is highly disorganised, has
sections with huge sinuses, and variation in blood vessel
diameter.
Typically, normal angiogenesis is triggered in adults at the site
of a major lesion/ cut. Tumours mimic the main physiological
features of wound tissue – one theory is that tumours are
wounds that never heal.
Normal angiogenesis is regulated by endogenous angiogenic
factors and inhibiters of angiogenesis:
Pro-angiogenesis - VEGF, bFGF, PDGF
Anti-angiogenesis – endostatin, angiostatin, thrombospondin
VEGF – Vascular Endothelial Growth Factor ; bFGF - basic
Fibroblast Growth Factor ; PDGF – Platelet-Derived Growth
Factor
When this balance is
tipped in tumour cells
(anti and pro factors
imbalanced), this
disorganised vasculature
occurs.
A simplified view of a
vascular network in
which all flow pathways are equivalent, as is often assumed. b |
A more realistic configuration, showing that blood flow
pathways are heterogeneous, with highly non-uniform lengths.
Arrows show blood flow directions in feeding and draining
vessels and illustrate the use of the terms 'proximal' and 'distal'
with regard to the circulatory system. Colours indicate the
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