Antagonist of nucleolin, N6L, inhibits neovascularization in mouse models of retinopathies.
Angiogenesis Inhibitors
/ pharmacology
Animals
Cell Proliferation
Choroidal Neovascularization
/ etiology
Disease Models, Animal
Intravitreal Injections
Mice
Mice, Inbred C57BL
Oxygen
/ adverse effects
Peptides
/ pharmacology
Phosphoproteins
/ antagonists & inhibitors
Phosphorylation
RNA-Binding Proteins
/ antagonists & inhibitors
Retinal Diseases
/ etiology
Nucleolin
angiogenesis
choroidal neovascularization (CNV)
nucleolin
oxygen-induced retinopathy (OIR)
vascular endothelial growth factor (VEGF)
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
25
07
2019
revised:
11
02
2020
accepted:
21
02
2020
pubmed:
7
3
2020
medline:
20
1
2021
entrez:
7
3
2020
Statut:
ppublish
Résumé
Retinal vascular diseases (RVD) have been identified as a major cause of blindness worldwide. These pathologies, including the wet form of age-related macular degeneration, retinopathy of prematurity, and diabetic retinopathy are currently treated by intravitreal delivery of anti-vascular endothelial growth factor (VEGF) agents. However, repeated intravitreal injections can lead to ocular complications and resistance to these treatments. Thus, there is a need to find new targeted therapies. Nucleolin regulates the endothelial cell (EC) activation and angiogenesis. In previous studies, we designed a pseudopeptide, N6L, that binds the nucleolin and blocks the tumor angiogenesis. In this study, the effect of N6L was investigated in two experimental models of retinopathies including oxygen-induced retinopathy (OIR) and choroidal neovascularization (CNV). We found that in mouse OIR, intraperitoneal injection of N6L is delivered to activated ECs and induced a 50% reduction of pathological neovascularization. The anti-angiogenic effect of N6L has been tested in CNV model in which the systemic injection of N6L induced a 33% reduction of angiogenesis. This effect is comparable to those obtained with VEGF-trap, a standard of care drug for RVD. Interestingly, with preventive and curative treatments, neoangiogenesis is inhibited by 59%. Our results have potential interest in the development of new therapies targeting other molecules than VEGF for RVD.
Identifiants
pubmed: 32141122
doi: 10.1096/fj.201901876R
doi:
Substances chimiques
Angiogenesis Inhibitors
0
N6L peptide
0
Peptides
0
Phosphoproteins
0
RNA-Binding Proteins
0
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5851-5862Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
Références
Al-Latayfeh M, Silva PS, Sun JK, Aiello LP. Antiangiogenic therapy for ischemic retinopathies. Cold Spring Harb Perspect Med. 2012;2:a006411.
Olsen TW, Lum F. Re: Wang et al.: incidence and risk factors for developing diabetic retinopathy among youths with type 1 or type 2 diabetes throughout the United States (Ophthalmology. 2017;124:424-430). Ophthalmology. 2017;124:e68-e69.
Fuma S, Nishinaka A, Inoue Y, et al. A pharmacological approach in newly established retinal vein occlusion model. Sci Rep. 2017;7:43509.
Campochiaro PA, Wykoff CC, Shapiro H, Rubio RG, Ehrlich JS. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014;121:1783-1789.
Keane PA, Sadda SR. Development of anti-VEGF therapies for intraocular use: a guide for clinicians. J Ophthalmol. 2012;2012:1-13.
Sampat KM, Garg SJ. Complications of intravitreal injections. Curr Opin Ophthalmol. 2010;21:178-183.
Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1102-1112.e1.
Berger CM, Gaume X, Bouvet P. The roles of nucleolin subcellular localization in cancer. Biochimie. 2015;113:78-85.
Destouches D, Khoury DE, Hamma-Kourbali Y, et al. Suppression of tumor growth and angiogenesis by a specific antagonist of the cell-surface expressed nucleolin. PLOS ONE. 2008;3:e2518.
Hovanessian AG, Soundaramourty C, Khoury DE, Nondier I, Svab J, Krust B. Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization. PLoS ONE. 2010;5:e15787.
Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol. 2003;163:871-878.
Leaderer D, Cashman SM, Kumar-Singh R. G-quartet oligonucleotide mediated delivery of proteins into photoreceptors and retinal pigment epithelium via intravitreal injection. Exp Eye Res. 2016;145:380-392.
Legrand D, Vigié K, Said EA, et al. Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. Eur J Biochem. 2004;271:303-317.
Tate A, Isotani S, Bradley MJ, et al. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells. BMC Cancer. 2006;6:197.
Take M, Tsutsui J, Obama H, et al. Identification of nucleolin as a binding protein for midkine (MK) and heparin-binding growth associated molecule (HB-GAM). J. Biochem. 1994;116:1063-1068.
Said EA, Courty J, Svab J, Delbé J, Krust B, Hovanessian AG. Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin. FEBS J. 2005;272:4646-4659.
Shi H, Huang Y, Zhou H, et al. Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin. Blood. 2007;110:2899-2906.
Sader M, Courty J, Destouches D. Nanoparticles functionalized with ligands of cell surface nucleolin for cancer therapy and diagnosis. J Nanomed Nanotechnol. 2015;6:310.
Destouches D, Page N, Hamma-Kourbali Y, et al. A simple approach to cancer therapy afforded by multivalent pseudopeptides that target cell-surface nucleoproteins. Cancer Res. 2011;71:3296-3305.
De Cola A, Franceschini M, Di Matteo A, et al. N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy. Cancer Lett. 2018;412:272-282.
Gilles M-E, Maione F, Cossutta M, et al. Nucleolin targeting impairs the progression of pancreatic cancer and promotes the normalization of tumor vasculature. Cancer Res. 2016;76:7181-7193.
Dhez A-C, Benedetti E, Antonosante A, et al. Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin. J Cell Physiol. 2018;233:4091-4105.
Diamantopoulou Z, Gilles M-E, Sader M, et al. Multivalent cationic pseudopeptide polyplexes as a tool for cancer therapy. Oncotarget. 2017;8:90108-90122.
Birmpas C, Briand JP, Courty J, Katsoris P. Nucleolin mediates the antiangiogenesis effect of the pseudopeptide N6L. BMC Cell Biol. 2012;13:32.
Stahl A, Connor KM, Sapieha P, et al. The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci. 2010;51:2813-2826.
Smith LE, Wesolowski E, McLellan A, et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35:101-111.
Montassar F, Darche M, Blaizot A, et al. Lebecetin, a C-type lectin, inhibits choroidal and retinal neovascularization. FASEB J. 2017;31:1107-1119.
Shao Z, Friedlander M, Hurst C, et al. Choroid sprouting assay: an ex vivo model of microvascular angiogenesis. PLoS One. 2013;8:e69552.
Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676-682.
Cossutta M, Darche M, Carpentier G, et al. Weibel-palade bodies orchestrate pericytes during angiogenesis. Arterioscler Thromb Vasc. 2019;39:1843-1858.
Connor KM, Krah NM, Dennison RJ, et al. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc. 2009;4:1565-1573.
Gioelli N, Maione F, Camillo C, et al. A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent. Sci Transl Med. 2018;10:eaah4807.
Sato T, Ooto S, Suzuki M, Spaide RF. Retinal pigment epithelial tear after intravitreal aflibercept for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina. 2015;46:87-90.
Storkebaum E, Carmeliet P. VEGF: a critical player in neurodegeneration. J. Clin. Invest. 2004;113:14-18.
Storkebaum E, Lambrechts D, Carmeliet P. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 2004;26:943-954.
Van Bergen T, Hu T-T, Etienne I, Reyns GE, Moons L, Feyen JHM. Neutralization of placental growth factor as a novel treatment option in diabetic retinopathy. Exp Eye Res. 2017;165:136-150.
Hovanessian AG, Puvion-Dutilleul F, Nisole S, et al. The cell-surface-expressed nucleolin is associated with the actin cytoskeleton. Exp Cell Res. 2000;261:312-328.
Turck N, Lefebvre O, Gross I, et al. Effect of laminin-1 on intestinal cell differentiation involves inhibition of nuclear nucleolin. J Cell Physiol. 2006;206:545-555.
Koutsioumpa M, Polytarchou C, Courty J, et al. Interplay between αvβ3 integrin and nucleolin regulates human endothelial and glioma cell migration. J Biol Chem. 2013;288:343-354.
Quiroz-Mercado J, Ramírez-Velázquez N, Partido G, et al. Tissue and cellular characterisation of nucleolin in a murine model of corneal angiogenesis. Graefes Arch Clin Exp Ophthalmol. 2016;254:1753-1763.
Bishop P. The biochemical structure of mammalian vitreous. Eye (Lond). 1996;10(Pt 6):664-670.
Destouches D, Huet E, Sader M, et al. Multivalent pseudopeptides targeting cell surface nucleoproteins inhibit cancer cell invasion through tissue inhibitor of metalloproteinases 3 (TIMP-3) release. J Biol Chem. 2012;287:43685-43693.
Ng DS, Yip YW, Bakthavatsalam M, et al. Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation. Sci Rep. 2017;7:45081.
Peters S, Cree IA, Alexander R, et al. Angiopoietin modulation of vascular endothelial growth factor: effects on retinal endothelial cell permeability. Cytokine. 2007;40:144-150.
Zhu X, Bai Y, Yu W, et al. The effects of pleiotrophin in proliferative diabetic retinopathy. PLoS One. 2015;10:e0115523.
Wang W, LeBlanc ME, Chen X, et al. Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease. Angiogenesis. 2017;20:479-492.
Presta M, Andrés G, Leali D, Dell'Era P, Ronca R. Inflammatory cells and chemokines sustain FGF2-induced angiogenesis. Eur Cytokine Netw. 2009;20:39-50.