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Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival.

Publication ,  Journal Article
Mi, J; Zhang, X; Giangrande, PH; McNamara, JO; Nimjee, SM; Sarraf-Yazdi, S; Sullenger, BA; Clary, BM
Published in: Biochem Biophys Res Commun
December 16, 2005

Alphavbeta3 integrin is a crucial factor involved in a variety of physiological processes, such as cell growth and migration, tumor invasion and metastasis, angiogenesis, and wound healing. Alphavbeta3 integrin exerts its effect by regulating endothelial cell (EC) migration, proliferation, and survival. Inhibiting the function of alphavbeta3 integrin, therefore, represents a potential anti-cancer, anti-thrombotic, and anti-inflammatory strategy. In this study, we tested an RNA aptamer, Apt-alphavbeta3 that binds recombinant alphavbeta3 integrin, for its ability to bind endogenous alphavbeta3 integrin on the surface of cells in culture and to subsequently affect cellular response. Our data illustrate that Apt-alphavbeta3 binds alphavbeta3 integrin expressed on the surface of live HUVECs. This interaction significantly decreases both basal and PDGF-induced cell proliferation as well as inhibition of cell adhesion. Apt-alphavbeta3 can also reduce PDGF-stimulated tube formation and increase HUVEC apoptosis through inhibition of FAK phosphorylation pathway. Our results demonstrate that by binding to its target, Apt-alphavbeta3 can efficiently inhibit human EC proliferation and survival, resulting in reduced angiogenesis. It predicts that Apt-alphavbeta3 could become useful in both tumor imaging and the treatment of tumor growth, atherosclerosis, thrombosis, and inflammation.

Duke Scholars

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Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

December 16, 2005

Volume

338

Issue

2

Start / End Page

956 / 963

Location

United States

Related Subject Headings

  • RNA
  • Integrin alphaVbeta3
  • Humans
  • Endothelial Cells
  • Drug Delivery Systems
  • Dose-Response Relationship, Drug
  • Cells, Cultured
  • Cell Survival
  • Cell Proliferation
  • Biochemistry & Molecular Biology
 

Citation

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Mi, J., Zhang, X., Giangrande, P. H., McNamara, J. O., Nimjee, S. M., Sarraf-Yazdi, S., … Clary, B. M. (2005). Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem Biophys Res Commun, 338(2), 956–963. https://doi.org/10.1016/j.bbrc.2005.10.043
Mi, Jing, Xiuwu Zhang, Paloma H. Giangrande, James O. McNamara, Shahid M. Nimjee, Shiva Sarraf-Yazdi, Bruce A. Sullenger, and Bryan M. Clary. “Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival.Biochem Biophys Res Commun 338, no. 2 (December 16, 2005): 956–63. https://doi.org/10.1016/j.bbrc.2005.10.043.
Mi J, Zhang X, Giangrande PH, McNamara JO, Nimjee SM, Sarraf-Yazdi S, et al. Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem Biophys Res Commun. 2005 Dec 16;338(2):956–63.
Mi, Jing, et al. “Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival.Biochem Biophys Res Commun, vol. 338, no. 2, Dec. 2005, pp. 956–63. Pubmed, doi:10.1016/j.bbrc.2005.10.043.
Mi J, Zhang X, Giangrande PH, McNamara JO, Nimjee SM, Sarraf-Yazdi S, Sullenger BA, Clary BM. Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem Biophys Res Commun. 2005 Dec 16;338(2):956–963.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

December 16, 2005

Volume

338

Issue

2

Start / End Page

956 / 963

Location

United States

Related Subject Headings

  • RNA
  • Integrin alphaVbeta3
  • Humans
  • Endothelial Cells
  • Drug Delivery Systems
  • Dose-Response Relationship, Drug
  • Cells, Cultured
  • Cell Survival
  • Cell Proliferation
  • Biochemistry & Molecular Biology