Tumor Vascular Permeability Factor Stimulates Endothelial Cell Growth and Angiogenesis

Tumor Vascular Permeability Factor Stimulates Endothelial Cell Growth and Angiogenesis

November 1989 | Daniel T. Connolly, Deborah M. Heuvelman, Rick Nelson, Jitka V. Olander, Barry L. Eppley, John J. Delfino, Ned R. Siegel, Richard M. Leimgruber, Joseph Feder
The vascular permeability factor (VPF), a 40-kD protein purified from guinea pig tumor cell conditioned medium, stimulates endothelial cell growth and angiogenesis. VPF increases vascular permeability when injected intradermally and promotes new blood vessel growth in healing rabbit bone grafts and rat corneas. The identity of VPF as the growth factor was confirmed through molecular weight analysis, amino acid sequence comparison, and immunoadsorption experiments. VPF binds specifically to endothelial cells and can be crosslinked to a high-molecular weight cell surface receptor, indicating direct interaction with endothelial cells. Unlike other endothelial cell growth factors, VPF does not stimulate thymidine incorporation or promote growth of other cell types such as mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angiogenesis. VPF was shown to stimulate endothelial cell growth in vitro and promote angiogenesis in vivo in two different model systems. The mitogenic activity of VPF was specific to vascular endothelial cells, as evidenced by its ability to stimulate [3H]thymidine incorporation in BAE cells but not in other cell types. VPF binds to a high-affinity cell surface receptor on endothelial cells, as demonstrated by affinity labeling experiments. VPF also induces angiogenesis in healing bone grafts and rat corneas, with lower doses inducing angiogenesis without inflammation. The study concludes that VPF is a specific endothelial cell mitogen that interacts directly with endothelial cells through a high-affinity receptor, and that its angiogenic activity may be related to its role in inflammation.The vascular permeability factor (VPF), a 40-kD protein purified from guinea pig tumor cell conditioned medium, stimulates endothelial cell growth and angiogenesis. VPF increases vascular permeability when injected intradermally and promotes new blood vessel growth in healing rabbit bone grafts and rat corneas. The identity of VPF as the growth factor was confirmed through molecular weight analysis, amino acid sequence comparison, and immunoadsorption experiments. VPF binds specifically to endothelial cells and can be crosslinked to a high-molecular weight cell surface receptor, indicating direct interaction with endothelial cells. Unlike other endothelial cell growth factors, VPF does not stimulate thymidine incorporation or promote growth of other cell types such as mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angiogenesis. VPF was shown to stimulate endothelial cell growth in vitro and promote angiogenesis in vivo in two different model systems. The mitogenic activity of VPF was specific to vascular endothelial cells, as evidenced by its ability to stimulate [3H]thymidine incorporation in BAE cells but not in other cell types. VPF binds to a high-affinity cell surface receptor on endothelial cells, as demonstrated by affinity labeling experiments. VPF also induces angiogenesis in healing bone grafts and rat corneas, with lower doses inducing angiogenesis without inflammation. The study concludes that VPF is a specific endothelial cell mitogen that interacts directly with endothelial cells through a high-affinity receptor, and that its angiogenic activity may be related to its role in inflammation.
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Understanding Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.