The integrin antagonist cilengitide activates αVβ3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells

PLoS ONE

Volumn 4, Issue 2, 2009, Pages

  Alghisi, Gian Carlo ^a   Ponsonnet, Lionel ^a   Rüegg, Curzio ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BETA1 INTEGRIN; CILENGITIDE; COLLAGEN TYPE 1; FIBRONECTIN; FOCAL ADHESION KINASE; PAXILLIN; PROTEIN TYROSINE KINASE; STEROID RECEPTOR COACTIVATOR 1; VASCULAR ENDOTHELIAL CADHERIN; VASCULOTROPIN; VITRONECTIN RECEPTOR;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL ACTIVATION; CELL ADHESION; CELL CULTURE; CELL JUNCTION; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; DRUG PROTEIN BINDING; ENDOTHELIUM CELL; ENZYME INHIBITION; HUMAN; HUMAN CELL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; UMBILICAL VEIN;

EID: 84887212399     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0004449     Document Type: Article

References (53)

1. Hynes RO (2007) Cell-matrix adhesion in vascular development. J Thromb Haemost 5 Suppl 1: 32-40.
2. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110: 673-687.
3. Alghisi GC, Rüegg C (2006) Vascular Integrins in Tumor Angiogenesis: Mediators and Therapeutic Targets. Endothelium 13: 113-135.
4. Kumar CC (2003) Integrin alphavbeta3 as a Therapeutic Target for Blocking Tumor-Induced Angiogenesis. Current Drug Targets 4: 123-131.
5. Smith J (2003) Cilengitide Merck. Curr Opin Investig Drugs 4: 741-745.
6. Dechantsreiter MA, Planker E, Matha B, Lohof E, Holzemann G, et al. (1999) N-Methylated cyclic RGD peptides as highly active and selective alphaVbeta3 integrin antagonists. J Med Chem 42: 3033-3040.
7. Nisato RE, Tille JC, Jonczyk A, Goodman SL, Pepper MS (2003) alphav beta 3 and alphav beta 5 integrin antagonists inhibit angiogenesis in vitro. Angiogenesis 6: 105-119.
8. Buerkle M, Pahernik S, Sutter A, Jonczyk A, Messmer K, et al. (2002) Inhibition of the alpha-V integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo. Br J Cancer 86: 788-795.
9. Yamada S, Bu XY, Khankaldyyan V, Gonzales-Gomez I, McComb JG, et al. (2006) Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice. Neurosurgery 59: 1304-1312.
10. Loges S, Butzal M, Otten J, Schweizer M, Fischer U, et al. (2007) Cilengitide inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. Biochem Biophys Res Commun 357: 1016-1020.
11. Mitjans F, Sander D, Adan J, Sutter A, Martinez JM, et al. (1995) An anti-alpha v-integrin antibody that blocks integrin function inhibits the development of a human melanoma in nude mice. J Cell Sci 108: 2825-2838.
12. MacDonald T, Taga T, Shimada H, Tabrizi P, Zlokovic B, et al. (2001) Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(v) integrin antagonist. Neurosurgery 48: 151-157.
13. Bieler G, Hasmim M, Monnier Y, Imaizumi N, Ameyar M, et al. (2007) Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-kappaB activation and endothelial cell survival. Oncogene 26: 5722-5732.
14. Tentori L, Dorio AS, Muzi A, Lacal PM, Ruffini F, et al. (2008) The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. Oncol Rep 19: 1039-1043.
15. Albert JM, Cao C, Geng L, Leavitt L, Hallahan DE, et al. (2006) Integrin alpha v beta 3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models. Int J Radiat Oncol Biol Phys 65: 1536-1543.
16. Hariharan S, Gustafson D, Holden S, McConkey D, Davis D, et al. (2007) Assessment of the biological and pharmacological effects of the alpha V beta3 and alpha V beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors. Ann Oncol 18: 1400-1407.
17. Nabors LB, Mikkelsen T, Rosenfeld SS, Hochberg F, Akella NS, et al. (2007) Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 25: 1651-1657.
18. Reardon DA, Fink KL, Mikkelsen T, Cloughesy TF, O'Neill A, et al. (2008) Randomized phase II study of cilengitide, an integrin-targeting arginine-glycinea-spartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 26: 5610-5617.
19. Friess H, Langrehr JM, Oettle H, Raedle J, Niedergethmann M, et al. (2006) A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer. BMC Cancer 6: 285.
20. Raguse JD, Gath HJ, Bier J, Riess H, Oettle H (2004) Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly vascularised head and neck tumour. Oral Oncol 40: 228-230.
21. Stupp R, Ruegg C (2007) Integrin Inhibitors Reaching the Clinic. J Clin Oncol 25: 1637-1638.
22. Brooks P, Montgomery A, Rosenfeld M, Reisfeld R, Hu T, et al. (1994) Integrin alphavbeta3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79: 1157-1164.
23. Zaric J, Ruegg C (2005) Integrin-mediated adhesion and soluble ligand cinding stabilize COX-2 protein levels in endothelial cells by Inducing expression and preventing degradation. J Biol Chem 280: 1077-1085.
24. Dormond O, Ponsonnet L, Hasmim M, Foletti A, Ruegg C (2004) Manganese-induced integrin affinity maturation promotes recruitment of alpha V beta 3 integrin to focal adhesions in endothelial cells: evidence for a role of phosphatidylinositol 3-kinase and Src. Thromb Haemost 92: 151-161.
25. Dejana E (2004) Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 5: 261-270.
26. Wang Y, Jin G, Miao H, Li JYS, Usami S, et al. (2006) Integrins regulate VE-cadherin and catenins: Dependence of this regulation on Src, but not on Ras. Proc Natl Acad Sci USA 103: 1774-1779.
27. Kevil CG, Payne DK, Mire E, Alexander JS (1998) Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins. J Biol Chem 273: 15099-15103.
28. Frelinger ALd, Du XP, Plow EF, Ginsberg MH (1991) Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function. J Biol Chem 266: 17106-17111.
29. Khaspekova SGVT, Lukin VV, Tikhomirov OIu, Berndt M, Kouns W, Mazurov AV (1996) Conformational changes of the platelet membrane glycoprotein IIb-IIIa complex stimulated by a monoclonal antibody to the N-terminal segment of glycoprotein IIIa. Biokhimiia 61: 412-428.
30. Xu W, Doshi A, Lei M, Eck MJ, Harrison SC (1999) Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell 3: 629-638.
31. Playford MP, Schaller MD (2004) The interplay between Src and integrins in normal and tumor biology. Oncogene 23: 7928-7946.
32. Calalb MB, Polte TR, Hanks SK (1995) Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases. Mol Cell Biol 15: 954-963.
33. Missbach M, Jeschke M, Feyen J, Muller K, Glatt M, et al. (1999) A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone 24: 437-449.
34. Wallez Y, Cand F, Cruzalegui F, Wernstedt C, Souchelnytskyi S, et al. (2006) Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site. Oncogene 26: 1067-1077.
35. Potter MD, Barbero S, Cheresh DA (2005) Tyrosine Phosphorylation of VE-cadherin Prevents Binding of p120- and beta-Catenin and Maintains the Cellular Mesenchymal State. J Biol Chem 280: 31906-31912.
36. Dejana E, Orsenigo F, Lampugnani MG (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 121: 2115-2122.
37. Ruegg C (1998) Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-g. Nat Med 4: 408-414.
38. Diaz-Gonzalez F, Forsyth J, Steiner B, Ginsberg MH (1996) Trans-dominant inhibition of integrin function. Mol Biol Cell 7: 1939-1951.
39. Calderwood DA, Tai V, Di Paolo G, De Camilli P, Ginsberg MH (2004) Competition for talin results in trans-dominant inhibition of integrin activation. J Biol Chem 279: 28889-28895.
40. Maubant S, Saint-Dizier D, Boutillon M, Perron-Sierra F, Casara PJ, et al. (2006) Blockade of alpha v beta3 and alpha v beta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells. Blood 108: 3035-3044.
41. Xiong JP, Goodman SL, Arnaout MA (2007) Purification, analysis, and crystal structure of integrins. Methods Enzymol 426: 307-336.
42. Takagi J, Petre BM, Walz T, Springer TA (2002) Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 110: 599-511.
43. Watson PM, Humphries MJ, Relton J, Rothwell NJ, Verkhratsky A, et al. (2007) Integrin-binding RGD peptides induce rapid intracellular calcium increases and MAPK signaling in cortical neurons. Mol Cell Neurosci 34: 147-154.
44. Umesh A, Thompson MA, Chini EN, Yip KP, Sham JS (2006) Integrin ligands mobilize Ca2+ from ryanodine receptor-gated stores and lysosome-related acidic organelles in pulmonary arterial smooth muscle cells. J Biol Chem 281: 34312-34323.
45. Tatone C, Carbone MC (2006) Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes. Reprod Biol Endocrinol 4: 48.
46. Arias-Salgado EG, Lizano S, Sarkar S, Brugge JS, Ginsberg MH, et al. (2003) Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci U S A 100: 13298-13302.
47. Wu MH, Ustinova E, Granger HJ (2001) Integrin binding to fibronectin and vitronectin maintains the barrier function of isolated porcine coronary venules. J Physiol 532: 785-791.
48. Qiao RL, Yan W, Lum H, Malik AB (1995) Arg-Gly-Asp peptide increases endothelial hydraulic conductivity: comparison with thrombin response. Am J Physiol Cell Physiol 269: C110-117.
49. Ma C, Rong Y, Radiloff DR, Datto MB, Centeno B, et al. (2008) Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev 22: 308-321.
50. Eliceiri BP, Puente XS, Hood JD, Stupack DG, Schlaepfer DD, et al. (2002) Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. J Cell Biol 157: 149-160.
51. Bezzi M, Hasmim M, Bieler G, Dormond O, Ruegg C (2003) Zoledronate Sensitizes Endothelial Cells to Tumor Necrosis Factor-induced Programmed Cell Death: evidence for the suppression of sustained activation of focal adhesion kinase and protein kinase B/Ak. J Biol Chem 278: 43603-43614.
52. Esser S, Lampugnani MG, Corada M, Dejana E, Risau W (1998) Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci 111: 1853-1865.
53. Wong V, Gumbiner BM (1997) A Synthetic Peptide Corresponding to the Extracellular Domain of Occludin Perturbs the Tight Junction Permeability Barrier. J Cell Biol 136: 399-409.