Figure 8.

The effects of vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibition in mouse models of breast cancer. Inhibition of the VE-PTP domain in endothelial cells activates Tie-2 signaling, in turn promoting a more stable vessel phenotype. In early tumor growth, this prevents early destabilization and hence slows the initial phase of tumor progression. In established tumors, vessels show structural and functional changes of normalization, resulting in improved tumor perfusion (which occurs because of an increased production of nitric oxide [NO] by endothelial nitric oxide synthase [eNOS]). In the setting of micrometastasis, stabilization of distant organ vessels prevents extravasation of tumor cells, delaying micrometastatic progression and prolonging survival.