Aberrant migration of smooth muscle cells (SMCs) is a key feature of restenosis. Since extracellular matrix proteins and their receptors of the integrin family play a critical role in this process, it is instrumental to understand their contribution to cell migration and invasive motility of SMC on the molecular level. Therefore, we investigated the role of χ-containing integrins expressed by primary human coronary artery smooth muscle cells (hCASMCs) in vitronectin (VN)-initiated signaling events and cell migration. In hCASMC plated on VN, α(v)-containing integrins were localized at focal adhesion sites, Haptotactic stimulation through VN led to a dose-dependent increase in cell migration and concomitantly to enhanced tyrosine phosphorylation Of focal adhesion kinase. Both events were completely blocked by a specific inhibitor of integrin χ(v) Additionally, the integrin 0(, inhibitor abolished PDGFBB-stimulated chemotactic migration. Confocal microscopy confirmed the increased tyrosine phosphorylation at VN-initiated focal contact sites in hCASMC, that was abolished upon χ(v), inhibition. In vitro invasion of hCASMC was severely compromised in the presence of the integrin α(v), inhibitor paralleled by decreased levels of secreted matrix metalloprotease 2 (MMP-2). Together, integrin α(v), inhibition abrogates tyrosine phosphorylation at focal adhesion sites and diminishes MMP-2 secretion leading to reduced migration and invasion of hCASMCs. © 2005 Elsevier Inc. All rights reserved.