STI-571 inhibits in vitro angiogenesis

Compounds that block angiogenesis are effective in the treatment of certain cancers and other angiogenesis-related diseases. Many of these compounds specifically target the rapidly proliferating and migrating endothelial cell. However, angiogenesis is a multi-faceted process involving heterotypic interactions between various cell types. For example, PDGFBB is an important cytokine secreted by endothelial cells that attracts smooth muscle cells to surround and stabilize a nascent vessel. Therefore, we hypothesized that STI-571, a tyrosine kinase inhibitor with PDGFβ receptor activity, would inhibit angiogenesis through an anti-migratory effect on smooth muscle cells. We demonstrate that STI-571 completely inhibits in vitro angiogenesis in fibrinogen-embedded mouse aorta. Furthermore, this angiostatic property was due mainly to an anti-migratory and anti-proliferative effect upon smooth muscle cells. These data suggest that STI-571, in addition to its efficacy in the treatment of certain cancers, may also prove to be clinically useful in diseases characterized by unregulated angiogenesis.