>> The presentation highlights that the anti-angiogenic effects of squalamine correlated well with squalamine induced blockade of the rapid vascular endothelial growth factor (VEGF) stimulated phosphorylation of p42/p44 MAP kinase in endothelial cells, an early cell response to activate proliferation. Squalamine also reduced VEGF induced phophorylation of focal adhesion kinase and stress activated protein kinase-2/p38, blocking in turn assembly of F-actin stress fibers in endothelial cells. These effects follow primary interaction of squalamine with caveolar domains at surface membranes of endothelial cells, sites for the concentration of vital signaling complexes to regulate the angiogenic process. The presentation concludes that the potent anti-tumor efficacy of squalamine is due to coordinated disruption of tumor associated angiogenesis. <<
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