Figure 8: Diagrams depicting cancer cells generating VEGF90K and shedding MVs with associated VEGF90K.

(a) VEGF165 is crosslinked by tTG to generate VEGF90K (top). MVs with associated VEGF90K are budding and shed from cancer cell plasma membrane (bottom). (b) Diagram depicting cancer cells shedding MVs with associated VEGF90K that engage recipient endothelial cells and activate VEGFRs, thereby promoting angiogenesis. MV-associated Hsp90 binds to VEGF90K, enabling the vesicles to activate VEGFRs on endothelial cells and stimulate the formation of new blood vessels. This stimulation is insensitive to Bevacizumab (top). 17AAG causes the release of VEGF90K from MVs. The free VEGF90K activates VEGFRs and stimulates angiogenesis but is sensitive to the inhibitory actions of Bevacizumab (bottom).