1. Inducing Angiogenesis
Nov 2, 2017

2. Hallmarks of Cancer, 2011

3. VEGF-A Signaling Pathway
VEGF = Vascular Endothelial Growth Factor

4. VEGF-A Isoforms

6. Functions of VEGF-A Isoforms
VEGF-165 will bind the coreceptor NRP for enhanced signaling
VEGF-121 or VEGF-110 will not bind

8. Angiogenesis and Inflammation
Tumor Microenvironment
Cytokines
Chemokines
Cell types

9. Cytokines
Soluble proteins that interact with cellular receptors involved with growth and activation of immune cells

10. Cyotkines VEGF family Axon Guidance factors -Slit-2 -Ephrin
Interleukins
Angiopoieins

11. Axon Guidance Factors, Slit-1
Double as inducers or inhibitors of angiogenesis
Slit-2, an axon guidance factor
-3 members, Slit-1, 2, 3
-Slit-2 binds to the Roundabout (Robo-4) receptor family
-possess pro-angiogenic properties, BUT inhibits migration of endothelial cells
-Results: Unclear

12. Axon Guidance Factors, Ephrin
8 have been identified in mammals
2 types: A and B
Type A:
-anchored to membrane by GPI
Type B:
-transmembrane domain
Src
Up regulation of Ephrin and their receptors in aggressive tumors

13. Interleukins IL-1α and IL-β ligands both bind to the IL-1 receptor
IL-1α is membrane bound
IL-β is secreted
IL-1 activation induces VEGF expression
in smooth muscule cells
IL-β also induces angiopoietin-1

14. Angiopoietins Four members of the angiopoietin family
Bind to Tie-2 receptor
Angiopoietin-1 is a regulator of endothelial cell stability and blood vessel permeability
Angiopoietin-1 is an angiogenic factor
Angiopoietin-2 competes for Tie-2 binding and functions as an inhibitor of angiogenesis

15. Angiopoietins