Inducing Angiogenesis Nov 2, 2017

Hallmarks of Cancer, 2011

VEGF-A Signaling Pathway VEGF = Vascular Endothelial Growth Factor

VEGF-A Isoforms

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

Angiogenesis and Inflammation Tumor Microenvironment Cytokines Chemokines Cell types

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

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

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

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

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

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

Angiopoietins