Genomes and Genes
Summary: An integrin that binds to a variety of plasma and extracellular matrix proteins containing the conserved RGD amino acid sequence and modulates cell adhesion. Integrin alphavbeta3 is highly expressed in OSTEOCLASTS where it may play role in BONE RESORPTION. It is also abundant in vascular smooth muscle and endothelial cells, and in some tumor cells, where it is involved in angiogenesis and cell migration. Although often referred to as the vitronectin receptor there is more than one receptor for vitronectin (RECEPTORS, VITRONECTIN).
- Tateishi U, Oka T, Inoue T. Radiolabeled RGD peptides as integrin alpha(v)beta3-targeted PET tracers. Curr Med Chem. 2012;19:3301-9 pubmed..Many linear or cyclic RGD peptides were developed for positron emission tomography (PET). In this review, we focused on currently developed RGD peptides as PET probes for non-invasive detection of integrin alpha(v)beta3 expression. ..
- Zhou Y, Kim Y, Chakraborty S, Shi J, Gao H, Liu S. 99mTc-labeled cyclic RGD peptides for noninvasive monitoring of tumor integrin ?V?3 expression. Mol Imaging. 2011;10:386-97 pubmed publisher..99mTc-3P-RGD2 has the capability to monitor integrin ?v?3 expression in a noninvasive fashion. ..
- Cam A, de Mejia E. RGD-peptide lunasin inhibits Akt-mediated NF-?B activation in human macrophages through interaction with the ?V?3 integrin. Mol Nutr Food Res. 2012;56:1569-81 pubmed publisher..Lunasin inhibited ?V?3 integrin-mediated proinflammatory markers and downregulated Akt-mediated NF-?B pathways through interaction with ?V?3 integrin. ..
- Mittra E, Goris M, Iagaru A, Kardan A, Burton L, Berganos R, et al. Pilot pharmacokinetic and dosimetric studies of (18)F-FPPRGD2: a PET radiopharmaceutical agent for imaging ?(v)?(3) integrin levels. Radiology. 2011;260:182-91 pubmed publisher..Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early. ..
- Ji S, Zhou Y, Voorbach M, Shao G, Zhang Y, Fox G, et al. Monitoring tumor response to linifanib therapy with SPECT/CT using the integrin ?v?3-targeted radiotracer 99mTc-3P-RGD2. J Pharmacol Exp Ther. 2013;346:251-8 pubmed publisher..Longitudinal imaging using (99m)Tc-3P-RGD2 SPECT/CT may be a useful tool for monitoring the downstream biologic effects of linifanib therapy. ..
- Xie P, Kondeti V, Lin S, Haruna Y, Raparia K, Kanwar Y. Role of extracellular matrix renal tubulo-interstitial nephritis antigen (TINag) in cell survival utilizing integrin (alpha)vbeta3/focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B-serine/threonine kinase (AKT) signali. J Biol Chem. 2011;286:34131-46 pubmed publisher..These in vivo and in vitro studies demonstrate an essential role of TINag in cellular survival to maintain proper tubular homeostasis utilizing integrin ?v?3 and downstream effectors. ..
- Cai H, Li Z, Huang C, Park R, Conti P. (64)Cu labeled AmBaSar-RGD2 for micro-PET imaging of integrin ?v?3 expression. Curr Radiopharm. 2011;4:68-74 pubmed..Therefore, the new tracer 64Cu-AmBaSar- RGD2 exhibited better tumor-targeting efficacy and more favorable in vivo pharmacokinetics than the 64Cu labeled RGD monomer due to the polyvalency effect. ..
- Shao G, Zhou Y, Wang F, Liu S. Monitoring glioma growth and tumor necrosis with the U-SPECT-II/CT scanner by targeting integrin ?v?3. Mol Imaging. 2013;12:39-48 pubmed..95. (99m)Tc-3P-RGD(2) SPECT/CT is excellent for monitoring ?(v)?(3) expression and tumor necrosis during tumor growth and may become a screening tool for patient selection before anti-?(v)?(3) therapy. ..
- Patsenker E, Popov Y, Stickel F, Schneider V, Ledermann M, Sägesser H, et al. Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis. Hepatology. 2009;50:1501-11 pubmed publisherThe vitronectin receptor integrin alphavbeta3 promotes angiogenesis by mediating migration and proliferation of endothelial cells, but also drives fibrogenic activation of hepatic stellate cells (HSCs) in vitro...
- Maupas Schwalm F, Bedel A, Auge N, Grazide M, Mucher E, Thiers J, et al. Integrin alpha(v)beta(3), metalloproteinases, and sphingomyelinase-2 mediate urokinase mitogenic effect. Cell Signal. 2009;21:1925-34 pubmed publisher..These findings highlight a new signaling mechanism for uPA, and suggest that, upon uPA stimulation, uPAR, MMPs, integrin alpha(v)beta(3) and NSMase-2 form a signaling complex that take part in mitogenic signaling in ECV304 cells. ..
- Lorger M, Krueger J, O Neal M, Staflin K, Felding Habermann B. Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci U S A. 2009;106:10666-71 pubmed publisher..Targeting this molecular mechanism could prove valuable for the inhibition of brain metastasis. ..
- Schottelius M, Laufer B, Kessler H, Wester H. Ligands for mapping alphavbeta3-integrin expression in vivo. Acc Chem Res. 2009;42:969-80 pubmed publisher..Other (18)F-labeled RGD analogues recently developed by Siemens and GE Healthcare have entered clinical trials. ..
- Kimura R, Levin A, Cochran F, Cochran J. Engineered cystine knot peptides that bind alphavbeta3, alphavbeta5, and alpha5beta1 integrins with low-nanomolar affinity. Proteins. 2009;77:359-69 pubmed publisher..Collectively, these data validate EETI-II as a scaffold for protein engineering, and highlight the development of unique integrin-binding peptides with potential for translational applications in cancer...
- Robinson S, Reynolds L, Kostourou V, Reynolds A, da Silva R, Tavora B, et al. Alphav beta3 integrin limits the contribution of neuropilin-1 to vascular endothelial growth factor-induced angiogenesis. J Biol Chem. 2009;284:33966-81 pubmed publisher..Our data suggest that beta3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2. ..
- Alghisi G, Ponsonnet L, Ruegg C. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells. PLoS ONE. 2009;4:e4449 pubmed publisher..These effects are potentially relevant to the clinical use of cilengitide as anticancer agent. ..
- Furundzija V, Fritzsche J, Kaufmann J, Meyborg H, Fleck E, Kappert K, et al. IGF-1 increases macrophage motility via PKC/p38-dependent alphavbeta3-integrin inside-out signaling. Biochem Biophys Res Commun. 2010;394:786-91 pubmed publisher..This involves activation of integrins and focal adhesion formation via inside-out PI3-kinase/PKC/p38-dependent signaling, but does not require MMP activation. ..
- Chetty C, Lakka S, Bhoopathi P, Rao J. MMP-2 alters VEGF expression via alphaVbeta3 integrin-mediated PI3K/AKT signaling in A549 lung cancer cells. Int J Cancer. 2010;127:1081-95 pubmed publisher..In summary, these data provide new insights into the mechanisms underlying MMP-2-mediated VEGF expression in lung tumor angiogenesis. ..
- Jia B, Liu Z, Zhu Z, Shi J, Jin X, Zhao H, et al. Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin ?v?3-selective radiotracer 99mTc-3PRGD 2 in non-human primates. Mol Imaging Biol. 2011;13:730-6 pubmed publisher..This tracer is safe and well tolerated, and no adverse events occurred in non-human primates. Further clinical testing and translation of (99m)Tc-3PRGD(2) for noninvasive imaging of integrin ?(v)?(3) in humans are warranted. ..
- Hayashida T, Jones J, Lee C, Schnaper H. Loss of beta1-integrin enhances TGF-beta1-induced collagen expression in epithelial cells via increased alphavbeta3-integrin and Rac1 activity. J Biol Chem. 2010;285:30741-51 pubmed publisher..Together, our results indicate that decreasing ?1 chain causes ?v?3-integrin to become functionally dominant and promotes renal cell fibrogenesis via Rac1-mediated ERK activity. ..
- Lössner D, Abou Ajram C, Benge A, Aumercier M, Schmitt M, Reuning U. Integrin alphavbeta3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription. J Cell Physiol. 2009;220:367-75 pubmed publisherWe previously showed that integrin alphavbeta3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells...
- Kluza E, van der Schaft D, Hautvast P, Mulder W, Mayo K, Griffioen A, et al. Synergistic targeting of alphavbeta3 integrin and galectin-1 with heteromultivalent paramagnetic liposomes for combined MR imaging and treatment of angiogenesis. Nano Lett. 2010;10:52-8 pubmed publisher..We show in vitro, using optical techniques and MRI, that the dual-targeting approach produces synergistic targeting effects, causing a dramatically elevated uptake of nanoparticles as compared to single ligand targeting. ..
- Makrigiannakis A, Karamouti M, Petsas G, Makris N, Nikas G, Antsaklis A. The expression of receptivity markers in the fallopian tube epithelium. Histochem Cell Biol. 2009;132:159-67 pubmed publisher..These results show for the first time the formation of pinopodes in the tubal epithelium at the time of endometrial receptivity and correlate it with the upregulation of the intact dimmer alpha v beta 3 in the tubes. ..
- Chen Y, Wei Y, Chen H, Fong Y, Hsu C, Tsai C, et al. Osteopontin increases migration and MMP-9 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells. J Cell Physiol. 2009;221:98-108 pubmed publisher..Taken together, our results indicated that OPN enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the alphavbeta3 integrin, FAK, MEK, ERK and NF-kappaB signal transduction pathway. ..
- Tang R, Long J, Chen B. [Expression of integrin alphavbeta3, tissue factor, and vascular endothelial growth factor in experimental choroidal neovascularization]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009;34:762-7 pubmedTo study the expression of vascular endothelial growth factor (VEGF), integrin alphavbeta3, and tissue factor (TF) in choroidal neovascularization (CNV). CNV was induced in 25 Brown Norway (BN) rats by diode laser with 532 nm wave length...
- Zannetti A, Del Vecchio S, Iommelli F, Del Gatto A, De Luca S, Zaccaro L, et al. Imaging of alpha(v)beta(3) expression by a bifunctional chimeric RGD peptide not cross-reacting with alpha(v)beta(5). Clin Cancer Res. 2009;15:5224-33 pubmed publisher..Our findings indicate that the novel chimeric Arg-Gly-Asp peptide, having no cross-reaction with alphavbeta5 integrin, allows highly selective alphavbeta3 expression imaging and monitoring. ..
- Liu S. Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem. 2009;20:2199-213 pubmed publisher..Improvement of tumor uptake and tumor-to-background ratios is important for early detection of integrin alpha(v)beta(3)-positive tumors and/or noninvasive monitoring of therapeutic efficacy of antiangiogenic therapy. ..
- Liu Z, Niu G, Wang F, Chen X. (68)Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging. Eur J Nucl Med Mol Imaging. 2009;36:1483-94 pubmed publisher..The favorable characterizations of (68)Ga-NOTA-RGD-BBN such as convenient synthesis, high specific activity, and high tumor uptake, warrant its further investigation for clinical cancer imaging. ..
- Merkel O, Germershaus O, Wada C, Tarcha P, Merdan T, Kissel T. Integrin alphaVbeta3 targeted gene delivery using RGD peptidomimetic conjugates with copolymers of PEGylated poly(ethylene imine). Bioconjug Chem. 2009;20:1270-80 pubmed publisher..The conjugates of PEG-PEI AB-block-copolymers with low ligand density of the RGD-mimetic appear to be promising candidates for in vivo cancer gene therapy. ..
- Verbisck N, Costa E, Costa F, Cavalher F, Costa M, Muras A, et al. ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis. Cancer Res. 2009;69:5546-52 pubmed publisher..Our results strongly support a functional role of ADAM23 during metastatic progression by negatively modulating alpha(v)beta(3) integrin activation. ..
- Bax D, Rodgers U, Bilek M, Weiss A. Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3. J Biol Chem. 2009;284:28616-23 pubmed publisher..The C-terminal GRKRK motif of tropoelastin can bind to cells in a divalent cation-dependent manner, identifying this as an integrin binding motif required for cell adhesion. ..
- Davis P, Davis F, Lin H, Mousa S, Zhou M, Luidens M. Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor. Am J Physiol Endocrinol Metab. 2009;297:E1238-46 pubmed publisherA thyroid hormone receptor on integrin alphavbeta3 that mediates cell surface-initiated nongenomic actions of thyroid hormone on tumor cell proliferation and on angiogenesis has been described...
- Bai J, Zhang J, Wu J, Shen L, Zeng J, Ding J, et al. JWA regulates melanoma metastasis by integrin alphaVbeta3 signaling. Oncogene. 2010;29:1227-37 pubmed publisher..These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma. ..
- Avalos A, Valdivia A, Muñoz N, Herrera Molina R, Tapia J, Lavandero S, et al. Neuronal Thy-1 induces astrocyte adhesion by engaging syndecan-4 in a cooperative interaction with alphavbeta3 integrin that activates PKCalpha and RhoA. J Cell Sci. 2009;122:3462-71 pubmed publisher..These observations are likely to be of widespread biological relevance because Thy-1-integrin binding is reportedly relevant to melanoma invasion, monocyte transmigration through endothelial cells and host defense mechanisms. ..
- Puklin Faucher E, Vogel V. Integrin activation dynamics between the RGD-binding site and the headpiece hinge. J Biol Chem. 2009;284:36557-68 pubmed publisher..become strengthened under force), as well as earlier evidence that Ca(2+) at the ADMIDAS results in lower binding affinity, these simulations provide a common structural model for the dynamic process by which integrins become activated. ..
- Pedroja B, Kang L, Imas A, Carmeliet P, Bernstein A. Plasminogen activator inhibitor-1 regulates integrin alphavbeta3 expression and autocrine transforming growth factor beta signaling. J Biol Chem. 2009;284:20708-17 pubmed publisher..PAI-1 induces the internalization of urokinase plasminogen activator/receptor and integrin alphavbeta3 from the cell surface...
- Vartak D, Lee B, Gemeinhart R. In vitro evaluation of functional interaction of integrin alphavbeta3 and matrix metalloprotease-2. Mol Pharm. 2009;6:1856-67 pubmed publisherb>Integrin alphavbeta3 and matrix metalloprotease-2 (MMP-2) are two established molecular targets of angiogenesis...
- Battle M, Goggi J, Allen L, Barnett J, Morrison M. Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled ?Vbeta3-integrin and ?V beta5-integrin imaging agent. J Nucl Med. 2011;52:424-30 pubmed publisher..These results suggest that this imaging agent may provide clinically important information for guiding patient care and monitoring the response to antiangiogenic therapy. ..
- Dumont R, Hildebrandt I, Su H, Haubner R, Reischl G, Czernin J, et al. Noninvasive imaging of alphaVbeta3 function as a predictor of the antimigratory and antiproliferative effects of dasatinib. Cancer Res. 2009;69:3173-9 pubmed publisher..50+/-17.68 mm(2) in controls; P=0.001). [(64)Cu]DOTA-c(RGDfK) may provide a sensitive means of monitoring tumor response to SFK inhibition in alpha(V)beta(3)-expressing cancers early in the course of therapy...
- Boles K, Schmieder A, Koch A, Carano R, Wu Y, Caruthers S, et al. MR angiogenesis imaging with Robo4- vs. alphaVbeta3-targeted nanoparticles in a B16/F10 mouse melanoma model. FASEB J. 2010;24:4262-70 pubmed publisher..0 T than Robo4. Noninvasive, neovascular assessments of the MR signal of Robo4, particularly combined with ?(V)?(3)-integrin expression, may help define tumor character prior to and following cancer therapy. ..
- Willmann J, Kimura R, Deshpande N, Lutz A, Cochran J, Gambhir S. Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast microbubbles conjugated to integrin-binding knottin peptides. J Nucl Med. 2010;51:433-40 pubmed publisher..Our results demonstrate that microbubbles conjugated to small peptide-targeting ligands provide imaging signals higher than those provided by a large antibody molecule. ..
- Morgan M, Byron A, Humphries M, Bass M. Giving off mixed signals--distinct functions of alpha5beta1 and alphavbeta3 integrins in regulating cell behaviour. IUBMB Life. 2009;61:731-8 pubmed publisher..By considering the GTPase and kinase signalling and trafficking of two such closely-related receptors, we begin to understand how cell migration is coordinated. ..
- Xie H, Diagaradjane P, Deorukhkar A, Goins B, Bao A, Phillips W, et al. Integrin ?v?3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy. Int J Nanomedicine. 2011;6:259-69 pubmed publisher..Active targeting of NSs to integrin ?v?3 offers the potential to increase accumulation preferentially in tumors and thereby enhance therapy efficacy...
- Chen W, Jarzyna P, van Tilborg G, Nguyen V, Cormode D, Klink A, et al. RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe. FASEB J. 2010;24:1689-99 pubmed publisher..This study demonstrates the ability to reroute HDL from its natural targets to tumor blood vessels and its potential for multimodal imaging of tumor-associated processes. ..