Targeting of αv integrins interferes with FAK activation and smooth muscle cell migration and invasion

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2005
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Varadarajulu, Jeeva
Laser, Martin
Hupp, Markus
Wu, Rongxue
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Biochemical and Biophysical Research Communications ; 331 (2005), 2. - pp. 404-412. - ISSN 0006-291X
Abstract
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 αv-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, αv-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 αv. Additionally, the integrin αv inhibitor abolished PDGF-BB-stimulated chemotactic migration. Confocal microscopy confirmed the increased tyrosine phosphorylation at VN-initiated focal contact sites in hCASMC, that was abolished upon αv inhibition. In vitro invasion of hCASMC was severely compromised in the presence of the integrin αv inhibitor paralleled by decreased levels of secreted matrix metalloprotease 2 (MMP-2). Together, integrin αv inhibition abrogates tyrosine phosphorylation at focal adhesion sites and diminishes MMP-2 secretion leading to reduced migration and invasion of hCASMCs.
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570 Biosciences, Biology
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Cell adhesion,Extracellular matrix proteins,Tyrosine phosphorylation,Vitronectin
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ISO 690VARADARAJULU, Jeeva, Martin LASER, Markus HUPP, Rongxue WU, Christof R. HAUCK, 2005. Targeting of αv integrins interferes with FAK activation and smooth muscle cell migration and invasion. In: Biochemical and Biophysical Research Communications. 331(2), pp. 404-412. ISSN 0006-291X. Available under: doi: 10.1016/j.bbrc.2005.03.175
BibTex
@article{Varadarajulu2005Targe-8427,
  year={2005},
  doi={10.1016/j.bbrc.2005.03.175},
  title={Targeting of αv integrins interferes with FAK activation and smooth muscle cell migration and invasion},
  number={2},
  volume={331},
  issn={0006-291X},
  journal={Biochemical and Biophysical Research Communications},
  pages={404--412},
  author={Varadarajulu, Jeeva and Laser, Martin and Hupp, Markus and Wu, Rongxue and Hauck, Christof R.}
}
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