A novel RGD antagonist that targets both αvβ3 and α5β1 induces apoptosis of angiogenic endothelial cells on type I collagen

Integrin αvβ3‐targeted cancer therapy

“…In addition to interacting with a number of ECM proteins, integrin α v β 3 has been shown to be associated with fibroblast growth factor-2 (FGF2), metalloproteinase MMP-2, activated PDGF, insulin, and VEGF receptors, facilitating the optimal activation of cell proliferation, invasion and preventing apoptosis [Kumar, 2003]. More importantly, the inhibition of α v β 3 integrin activity by monoclonal antibodies (mAbs), cyclic RGD peptide antagonists, and peptidomimetics has been shown to induce endothelial cell apoptosis [Meerovitch et al, 2003] and to inhibit angiogenesis [Kumar, 2003].…”

In vitro and In vivo Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin αvβ3

“…Integrins, a family of cell adhesion molecules composed of noncovalently associated a and h subunits, are involved in a wide range of cell-ECM and cell-cell interactions (4)(5)(6). Inhibition of a v integrin activity by monoclonal antibodies (mAb), cyclic RGD peptide antagonists, and peptidomimetics has been shown to induce endothelial cell apoptosis, to inhibit angiogenesis, and to increase endothelial monolayer permeability (7,8). The a v h 3 integrin, which recruits and activates matrix metalloproteinase-2 and plasmin to degrade the basement membrane and interstitial matrix (9), is significantly up-regulated on endothelium during angiogenesis but not in quiescent endothelium (4,5,7).…”

Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway

“…Integrin a 1 h 1 and a 2 h 1 mediate cell adhesion on collagen, which is a critical step in initiating tube formation of endothelial cells (20), whereas recruitment of integrin a 5 h 1 , the fibronectin receptor, is required for cell migration in the process of angiogenesis. In the present study, we showed that terbinafine at a concentration of 120 Amol/L caused a 50% inhibition in the adhesion of endothelial cells on collagen-or fibronectin-coated plates (Fig.…”