Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival.
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.
Mi
Jing
J
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Zhang
Xiuwu
X
Giangrande
Paloma H
PH
McNamara
James O
JO
Nimjee
Shahid M
SM
Sarraf-Yazdi
Shiva
S
Sullenger
Bruce A
BA
Clary
Bryan M
BM
D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D012313:RNA / Q000008:administration & dosage*
D052157:Aptamers, Nucleotide; D039302:Integrin alphaVbeta3; D012313:RNA