Regulation of tumor angiogenesis and choroidal neovascularization by endogenous angioinhibitors

Journal of Cancer Science and Therapy

Volumn 5, Issue 12, 2013, Pages 417-426

  Gunda, Venugopal ^a   Sudhakar, Yakkanti Akul ^b  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b SRI INTERNATIONAL   (United States)

Author keywords

Angiogenesis; Endothelial progenitor cells (EPCs); Pigment epithelium derived factor (PEDF); Vasoinhibins

Indexed keywords

ANGIOGENESIS INHIBITOR; ANGIOPOIETIN; ANGIOSTATIN; CANSTATIN; COLLAGEN TYPE 4; CYCLOOXYGENASE 2; ENDOREPELLIN; FIBROBLAST GROWTH FACTOR; GELATINASE A; GELATINASE B; HEXASTATIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTEGRIN; METICRANE; NYSTATIN PLUS TETRACYCLINE; PENTASTATIN; PIGMENT EPITHELIUM DERIVED FACTOR; SCATTER FACTOR; THROMBOSPONDIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR; TUMSTATIN; UNCLASSIFIED DRUG; VASCULOTROPIN; VASOINHIBIN;

ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ENDOTHELIUM CELL; HUMAN; INTRACELLULAR SIGNALING; NEOPLASM; NONHUMAN; RETINA MACULA AGE RELATED DEGENERATION; REVIEW; SIGNAL TRANSDUCTION; SUBRETINAL NEOVASCULARIZATION; TUMOR GROWTH;

EID: 84893138802     PISSN: None     EISSN: 19485956     Source Type: Journal    
DOI: 10.4172/1948-5956.1000235     Document Type: Review

References (112)

1. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, et al. (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56: 549-580.
2. Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7: 452-464.
3. Nakatsu MN, Sainson RC, Aoto JN, Taylor KL, Aitkenhead M, et al. (2003) Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels: the role of fibroblasts and Angiopoietin-1. Microvasc Res 66: 102-112.
4. Asahara T, Kawamoto A (2004) Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol 287: C572-579.
5. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182-1186.
6. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307: 58-62.
7. Alon T, Hemo I, Itin A, Pe'er J, Stone J, et al. (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1: 1024-1028.
8. Grossniklaus HE, Ling JX, Wallace TM, Dithmar S, Lawson DH, et al. (2002) Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis 8: 119-126.
9. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146: 1029-1039.
10. Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108: 2369-2379.
11. Lu M, Adamis AP (2006) Molecular biology of choroidal neovascularization. Ophthalmol Clin North Am 19: 323-334.
12. Sudhakar A, Kalluri R (2010) Molecular mechanisms of angiostatis. Encyclopedia of the eye 3 M-P: 52-59.
13. Siemerink MJ, Augustin AJ, Schlingemann RO (2010) Mechanisms of ocular angiogenesis and its molecular mediators. Dev Ophthalmol 46: 4-20.
14. Sudhakar A, Nyberg P, Keshamouni VG, Mannam AP, Li J, et al. (2005) Human alpha1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by alpha1beta1 integrin. J Clin Invest 115: 2801-2810.
15. Maeshima Y, Sudhakar A, Lively JC, Ueki K, Kharbanda S, et al. (2002) Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 295: 140-143.
16. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407: 249-257.
17. Kalluri R (2003) Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer 3: 422-433.
18. Humphries JD, Byron A, Humphries MJ (2006) Integrin ligands at a glance. J Cell Sci 119: 3901-3903.
19. Stupack DG, Cheresh DA (2002) Get a ligand, get a life: integrins, signaling and cell survival. J Cell Sci 115: 3729-3738.
20. Stupack DG, Cheresh DA (2002) ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci STKE 2002: pe7.
21. Cheresh DA, Stupack DG (2002) Integrin-mediated death: an explanation of the integrin-knockout phenotype? Nat Med 8: 193-194.
22. Boosani CS, Mannam AP, Cosgrove D, Silva R, Hodivala-Dilke KM, et al. (2007) Regulation of COX-2 mediated signaling by alpha3 type IV noncollagenous domain in tumor angiogenesis. Blood 110: 1168-1177.
23. Qazi Y, Maddula S, Ambati BK (2009) Mediators of ocular angiogenesis. J Genet 88: 495-515.
24. Sato Y (2000) Molecular mechanism of angiogenesis transcription factors and their therapeutic relevance. Pharmacol Ther 87: 51-60.
25. Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8: 604-617.
26. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2: 161-174.
27. Oklu R, Walker TG, Wicky S, Hesketh R (2010) Angiogenesis and current antiangiogenic strategies for the treatment of cancer. J Vasc Interv Radiol 21: 1791-1805.
28. Mettouchi A, Meneguzzi G (2006) Distinct roles of beta1 integrins during angiogenesis. Eur J Cell Biol 85: 243-247.
29. Li M, Wu ZM, Yang H, Huang SJ (2011) NFÎoB and JNK/MAPK activation mediates the production of major macrophage-or dendritic cell-recruiting chemokine in human first trimester decidual cells in response to proinflammatory stimuli. J Clin Endocrinol Metab 96: 2502-2511.
30. Aurora AB, Biyashev D, Mirochnik Y, Zaichuk TA, Sánchez-Martinez C, et al. (2010) NF-kappaB balances vascular regression and angiogenesis via chromatin remodeling and NFAT displacement. Blood 116: 475-484.
31. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8: 221-233.
32. van Hinsbergh VW, Koolwijk P (2008) Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res 78: 203-212.
33. Newby AC (2005) Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 85: 1-31.
34. Pozzi A, LeVine WF, Gardner HA (2002) Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis. Oncogene 21: 272-281.
35. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25: 9-34.
36. Chau KY, Sivaprasad S, Patel N, Donaldson TA, Luthert PJ, et al. (2008) Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in age-related macular degeneration. Eye (Lond) 22: 855-859.
37. Alge-Priglinger CS, Kreutzer T, Obholzer K, Wolf A, Mempel M, et al. (2009) Oxidative stress-mediated induction of MMP-1 and MMP-3 in human RPE cells. Invest Ophthalmol Vis Sci 50: 5495-5503.
38. Marron MB, Singh H, Tahir TA, Kavumkal J, Kim HZ, et al. (2007) Regulated proteolytic processing of Tie1 modulates ligand responsiveness of the receptor-tyrosine kinase Tie2. J Biol Chem 282: 30509-30517.
39. Gridley T (2007) Notch signaling in vascular development and physiology. Development 134: 2709-2718.
40. Nyberg P, Xie L, Kalluri R (2005) Endogenous inhibitors of angiogenesis. Cancer Res 65: 3967-3979.
41. Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6: 273-286.
42. Folkman J (2007) Is angiogenesis an organizing principle in biology and medicine? J Pediatr Surg 42: 1-11.
43. Davis GE, Senger DR (2005) Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 97: 1093-1107.
44. Clamp AR, Jayson GC (2005) The clinical potential of antiangiogenic fragments of extracellular matrix proteins. Br J Cancer 93: 967-972.
45. Colorado PC, Torre A, Kamphaus G, Maeshima Y, Hopfer H, et al. (2000) Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res 60: 2520-2526.
46. Nyberg P, Xie L, Sugimoto H, Colorado P, Sund M, et al. (2008) Characterization of the anti-angiogenic properties of arresten, an alpha1beta1 integrin-dependent collagen-derived tumor suppressor. Exp Cell Res 314: 3292-3305.
47. Boosani CS, Nalabothula N, Sheibani N, Sudhakar A (2010) Inhibitory effects of arresten on bFGF-induced proliferation, migration, and matrix metalloproteinase-2 activation in mouse retinal endothelial cells. Curr Eye Res 35: 45-55.
48. Magnon C, Galaup A, Mullan B, Rouffiac V, Bouquet C, et al. (2005) Canstatin acts on endothelial and tumor cells via mitochondrial damage initiated through interaction with alphavbeta3 and alphavbeta5 integrins. Cancer Res 65: 4353-4361.
49. Magnon C, Opolon P, Ricard M, Connault E, Ardouin P, et al. (2007) Radiation and inhibition of angiogenesis by canstatin synergize to induce HIF-1alpha-mediated tumor apoptotic switch. J Clin Invest 117: 1844-1855.
50. Petitclerc E, Boutaud A, Prestayko A, Xu J, Sado Y, et al. (2000) New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo. J Biol Chem 275: 8051-8061.
51. Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, et al. (2000) Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 275: 1209-1215.
52. Magnon C, Opolon P, Connault E, Mir LM, Perricaudet M, et al. (2008) Canstatin gene electrotransfer combined with radiotherapy: preclinical trials for cancer treatment. Gene Ther 15: 1436-1445.
53. Narazaki M, Tosato G (2006) Canstatin: an inhibitor of angiogenesis and tumor growth revisited. Cancer J 12: 110-112.
54. Panka DJ, Mier JW (2003) Canstatin inhibits Akt activation and induces Fas-dependent apoptosis in endothelial cells. J Biol Chem 278: 37632-37636.
55. Lima E Silva R, Kachi S, Akiyama H, Shen J, Aslam S, et al. (2006) Recombinant non-collagenous domain of alpha2(IV) collagen causes involution of choroidal neovascularization by inducing apoptosis. J Cell Physiol 208: 161-166.
56. Wang Y, Yin H, Chen P, Xie L, Wang Y (2011) Inhibitory effect of canstatin in alkali burn-induced corneal neovascularization. Ophthalmic Res 46: 66-72.
57. Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, et al. (2003) Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell 3: 589-601.
58. Monboisse JC, Garnotel R, Bellon G, Ohno N, Perreau C, et al. (1994) The alpha 3 chain of type IV collagen prevents activation of human polymorphonuclear leukocytes. J Biol Chem 269: 25475-25482.
59. Sudhakar A, Sugimoto H, Yang C, Lively J, Zeisberg M, et al. (2003) Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha vbeta 3 and alpha 5beta 1 integrins. Proc Natl Acad Sci U S A 100: 4766-4771.
60. Maeshima Y, Colorado PC, Torre A, Holthaus KA, Grunkemeyer JA, et al. (2000) Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem 275: 21340-21348.
61. Maeshima Y, Yerramalla UL, Dhanabal M, Holthaus KA, Barbashov S, et al. (2001) Extracellular matrix-derived peptide binds to alpha(v)beta(3) integrin and inhibits angiogenesis. J Biol Chem 276: 31959-31968.
62. Goto T, Ishikawa H, Matsumoto K, Nishimura D, Kusaba M, et al. (2008) Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis. Int J Oncol 33: 33-40.
63. Chung IS, Son YI, Ko YJ, Baek CH, Cho JK, et al. (2008) Peritumor injections of purified tumstatin delay tumor growth and lymphatic metastasis in an orthotopic oral squamous cell carcinoma model. Oral Oncol 44: 1118-1126.
64. Pasco S, Brassart B, Ramont L, Maquart FX, Monboisse JC (2005) Control of melanoma cell invasion by type IV collagen. Cancer Detect Prev 29: 260-266.
65. Zhang GM, Sui LH, Jia T, Zhao YZ, Fu SB, et al. (2008) [Inhibitory effect of recombinant anti-angiogenic peptide of tumstatin on growth and metastasis of human ovarian cancer transplanted in nude mice]. Zhonghua Zhong Liu Za Zhi 30: 170-173.
66. Mundel TM, Yliniemi AM, Maeshima Y, Sugimoto H, Kieran M, et al. (2008) Type IV collagen alpha6 chain-derived noncollagenous domain 1 (alpha6(IV) NC1) inhibits angiogenesis and tumor growth. Int J Cancer 122: 1738-1744.
67. Gunda V, Verma RK, Sudhakar AY (2013) Inhibition of Elastin Peptide-Mediated Angiogenic Signaling Mechanism(s) in Choroidal Endothelial Cells by the a6(IV)NC1 Collagen Fragment. Invest Ophthalmol Vis Sci (Publication ahead of print: accepted).
68. Karagiannis ED, Popel AS (2007) Identification of novel short peptides derived from the alpha 4, alpha 5, and alpha 6 fibrils of type IV collagen with anti-angiogenic properties. Biochem Biophys Res Commun 354: 434-439.
69. Koskimaki JE, Karagiannis ED, Tang BC, Hammers H, Watkins DN, et al. (2010) Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model. BMC Cancer 10: 29.
70. Felbor U, Dreier L, Bryant RA, Ploegh HL, Olsen BR, et al. (2000) Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J 19: 1187-1194.
71. Ricard-Blum S, Féraud O, Lortat-Jacob H, Rencurosi A, Fukai N, et al. (2004) Characterization of endostatin binding to heparin and heparan sulfate by surface plasmon resonance and molecular modeling: role of divalent cations. J Biol Chem 279: 2927-2936.
72. Wickström SA, Alitalo K, Keski-Oja J (2002) Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. Cancer Res 62: 5580-5589.
73. Wickström SA, Alitalo K, Keski-Oja J (2003) Endostatin associates with lipid rafts and induces reorganization of the actin cytoskeleton via down-regulation of RhoA activity. J Biol Chem 278: 37895-37901.
74. Ling Y, Yang Y, Lu N, You QD, Wang S, et al. (2007) Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells. Biochem Biophys Res Commun 361: 79-84.
75. Abdollahi A, Hahnfeldt P, Maercker C, Gröne HJ, Debus J, et al. (2004) Endostatin's antiangiogenic signaling network. Mol Cell 13: 649-663.
76. Hanai J, Gloy J, Karumanchi SA, Kale S, Tang J, et al. (2002) Endostatin is a potential inhibitor of Wnt signaling. J Cell Biol 158: 529-539.
77. Hanai J, Dhanabal M, Karumanchi SA, Albanese C, Waterman M, et al. (2002) Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1. J Biol Chem 277: 16464-16469.
78. Bhutto IA, Uno K, Merges C, Zhang L, McLeod DS, et al. (2008) Reduction of endogenous angiogenesis inhibitors in Bruch's membrane of the submacular region in eyes with age-related macular degeneration. Arch Ophthalmol 126: 670-678.
79. Fukai N, Eklund L, Marneros AG, Oh SP, Keene DR, et al. (2002) Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J 21: 1535-1544.
80. Hayashi M, Tamura Y, Dohmae N, Kojima S, Shimonaka M (2008) Plasminogen N-terminal activation peptide modulates the activity of angiostatin-related peptides on endothelial cell proliferation and migration. Biochem Biophys Res Commun 369: 635-640.
81. Burwick NR, Wahl ML, Fang J, Zhong Z, Moser TL, et al. (2005) An Inhibitor of the F1 subunit of ATP synthase (IF1) modulates the activity of angiostatin on the endothelial cell surface. J Biol Chem 280: 1740-1745.
82. Tarui T, Miles LA, Takada Y (2001) Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells. J Biol Chem 276: 39562-39568.
83. Shantha Kumara HM, Tohme ST, Yan X, Nasar A, Senagore AJ, et al. (2011) Plasma levels of angiostatin and endostatin remain unchanged for the first 3 weeks after colorectal cancer surgery. Surg Endosc 25: 1939-1944.
84. Tysome JR, Wang P, Alusi G, Briat A, Gangeswaran R, et al. (2011) Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene: an oncolytic virus superior to dl1520 (ONYX-015) for human head and neck cancer. Hum Gene Ther 22: 1101-1108.
85. Lai CC, Wu WC, Chen SL, Xiao X, Tsai TC, et al. (2001) Suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. Invest Ophthalmol Vis Sci 42: 2401-2407.
86. Bornstein P (2001) Thrombospondins as matricellular modulators of cell function. J Clin Invest 107: 929-934.
87. Bornstein P (2009) Thrombospondins function as regulators of angiogenesis. J Cell Commun Signal 3: 189-200.
88. Dawson DW, Pearce SF, Zhong R, Silverstein RL, Frazier WA, et al. (1997) CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol 138: 707-717.
89. Kaur S, Kuznetsova SA, Pendrak ML, Sipes JM, Romeo MJ, et al. (2011) Heparan sulfate modification of the transmembrane receptor CD47 is necessary for inhibition of T cell receptor signaling by thrombospondin-1. J Biol Chem 286: 14991-15002.
90. Fitchev PP, Wcislak SM, Lee C, Bergh A, Brendler CB, et al. (2010) Thrombospondin-1 regulates the normal prostate in vivo through angiogenesis and TGF-beta activation. Lab Invest 90: 1078-1090.
91. Krady MM, Zeng J, Yu J, MacLauchlan S, Skokos EA, et al. (2008) Thrombospondin-2 modulates extracellular matrix remodeling during physiological angiogenesis. Am J Pathol 173: 879-891.
92. Lopez-Dee Z, Pidcock K, Gutierrez LS (2011) Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm 2011: 296069.
93. Aviezer D, Hecht D, Safran M, Eisinger M, David G, et al. (1994) Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis. Cell 79: 1005-1013.
94. Bix G, Fu J, Gonzalez EM, Macro L, Barker A, et al. (2004) Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin. J Cell Biol 166: 97-109.
95. Goyal A, Pal N, Concannon M, Paul M, Doran M, et al. (2011) Endorepellin, the angiostatic module of perlecan, interacts with both the α2Î21 integrin and vascular endothelial growth factor receptor 2 (VEGFR2): a dual receptor antagonism. J Biol Chem 286: 25947-25962.
96. Nyström A, Shaik ZP, Gullberg D, Krieg T, Eckes B, et al. (2009) Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin angiostatic activity. Blood 114: 4897-4906.
97. Gonzalez EM, Reed CC, Bix G, Fu J, Zhang Y, et al. (2005) BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan. J Biol Chem 280: 7080-7087.
98. Bix G, Castello R, Burrows M, Zoeller JJ, Weech M, et al. (2006) Endorepellin in vivo: targeting the tumor vasculature and retarding cancer growth and metabolism. J Natl Cancer Inst 98: 1634-1646.
99. Clapp C, Thebault S, Arnold E, García C, Rivera JC, et al. (2008) Vasoinhibins: novel inhibitors of ocular angiogenesis. Am J Physiol Endocrinol Metab 295: E772-778.
100. D'Angelo G, Struman I, Martial J, Weiner RI (1995) Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin. Proc Natl Acad Sci U S A 92: 6374-6378.
101. Gonzalez C, Corbacho AM, Eiserich JP, Garcia C, Lopez-Barrera F, et al. (2004) 16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. Endocrinology 145: 5714-5722.
102. Ziche M, Morbidelli L (2000) Nitric oxide and angiogenesis. J Neurooncol 50: 139-148.
103. Martini JF, Piot C, Humeau LM, Struman I, Martial JA, et al. (2000) The antiangiogenic factor 16K PRL induces programmed cell death in endothelial cells by caspase activation. Mol Endocrinol 14: 1536-1549.
104. Tabruyn SP, Sorlet CM, Rentier-Delrue F, Bours V, Weiner RI, et al. (2003) The antiangiogenic factor 16K human prolactin induces caspase-dependent apoptosis by a mechanism that requires activation of nuclear factor-kappaB. Mol Endocrinol 17: 1815-1823.
105. Zhou SY, Xie ZL, Xiao O, Yang XR, Heng BC, et al. (2010) Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant adenovirus encoding human vasohibin-1. Mol Vis 16: 1389-1398.
106. Clapp C, Aranda J, González C, Jeziorski MC, Martínez de la Escalera G (2006) Vasoinhibins: endogenous regulators of angiogenesis and vascular function. Trends Endocrinol Metab 17: 301-307.
107. Tombran-Tink J, Chader GG, Johnson LV (1991) PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res 53: 411-414.
108. Ho TC, Chen SL, Yang YC, Liao CL, Cheng HC, et al. (2007) PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells. Cardiovasc Res 76: 213-223.
109. Zhou XY, Liao Q, Pu YM, Tang YQ, Gong X, et al. (2009) Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization. Chin Med J (Engl) 122: 2711-2717.
110. Gehlbach P, Demetriades AM, Yamamoto S, Deering T, Duh EJ, et al. (2003) Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization. Gene Ther 10: 637-646.
111. Gehlbach P, Demetriades AM, Yamamoto S, Deering T, Xiao WH, et al. (2003) Periocular gene transfer of sFlt-1 suppresses ocular neovascularization and vascular endothelial growth factor-induced breakdown of the blood-retinal barrier. Hum Gene Ther 14: 129-141.
112. Apte RS, Barreiro RA, Duh E, Volpert O, Ferguson TA (2004) Stimulation of neovascularization by the anti-angiogenic factor PEDF. Invest Ophthalmol Vis Sci 45: 4491-4497.