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Serpins in Angiogenesis

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Angiogenesis and Vascularisation

Abstract

Serpins (serine proteinase inhibitors) are the largest superfamily of protease inhibitors. The serpins are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Most of them act as classical protease inhibitors, but there are also serpins that inhibit other types of proteinases, e.g., caspases, or have different, noninhibitory functions, e.g., hormone transport. Serpins are involved in regulation of numerous biological pathways that initiate inflammation, coagulation, fibrinolysis, complement activation responses, apoptosis, extracellular matrix composition, and angiogenesis. The following serpins have been identified as potential regulators of angiogenesis: plasminogen activator inhibitor type 1 (PAI-1), kallistatin, protein C inhibitor, angiotensinogen, maspin, antithrombin, nexin-1, and pigment epithelial-derived factor. They exert mainly antiangiogenic activity, by inhibition of proteolytic processes in which serine proteases and matrix metalloproteinases (MMPs) are key players. Among them, PAI-1 appears to be the most controversial serpin in angiogenesis; it may act both as a pro- and antiangiogenic factor, depending upon the type of cells and existing conditions. Taken together, serpins remarkably contribute to vessels formation process; they are able to affect more than one of the angiogenic steps and their activity extend beyond the inhibition of target proteinases.

Professor Czeslaw Cierniewski has died on 24th October, 2013

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References

  1. Irving JA, Pike RN, Lusk AM, Whisstock JC (2000) Phylogeny of the serpent super family: implications of patterns of amino acid conservation for structure and function. Genome Res 10:1845–1864

    CAS  PubMed  Google Scholar 

  2. Law RH, Zhang Q, McGowan S, Buckle AM, Silverman GA, Wong W, Rosado CJ, Langendorf CG, Pike RN, Bird PI, Whisstock JC (2006) An overview of the serpin superfamily. Genome Biol 7:216–226

    PubMed Central  PubMed  Google Scholar 

  3. Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, Irving JA, Lomas DA, Luke CJ, Moyer RW, Pemberton PA, Remold-O’Donnell E, Salvesen GS, Travis J, Whisstock JC (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 276:33293–33296

    CAS  PubMed  Google Scholar 

  4. Potempa J, Korzus E, Travis J (1994) The serpin superfamily of proteinase inhibitors: structure, function, and regulation. J Biol Chem 269:15957–15960

    CAS  PubMed  Google Scholar 

  5. Irving JA, Pike RN, Dai W, Bromme D, Worrall DM, Silverman GA, Coetzer TH, Dennison C, Bottomley SP, Whisstock JC (2002) Evidence that serpin architecture intrinsically supports papain-like cysteine protease inhibition: engineering alpha(1)-antitrypsin to inhibit cathepsin proteases. Biochemistry 41:4998–5004

    CAS  PubMed  Google Scholar 

  6. Pemberton PA, Stein PE, Pepys MB, Potter JM, Carrell RW (1988) Hormone binding globulins undergo serpin conformational change in inflammation. Nature 336:257–258

    CAS  PubMed  Google Scholar 

  7. Nagata K (1996) Hsp47: a collagen-specific molecular chaperone. Trends Biochem Sci 21:22–26

    CAS  PubMed  Google Scholar 

  8. Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E, Sager R (1994) Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263:526–529

    CAS  PubMed  Google Scholar 

  9. Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu HJ, Benedict W, Bouck NP (1999) Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285:245–248

    CAS  PubMed  Google Scholar 

  10. Corvol P, Lamande N, Cruz A, Celerier J, Gasc JM (2003) Inhibition of angiogenesis: a new function for angiotensinogen and des(angiotensin I)angiotensinogen. Curr Hypertens Rep 5:149–154

    PubMed  Google Scholar 

  11. Gettins PGW (2002) Serpin structure, mechanism and function. Chem Rev 102:4751–4803

    CAS  PubMed  Google Scholar 

  12. Zhou A, Carrell RW, Huntington JA (2001) The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop. J Biol Chem 276:27541–27547

    CAS  PubMed  Google Scholar 

  13. Huntington JA, Read RJ, Carrell RW (2000) Structure of a serpin-protease complex shows inhibition by deformation. Nature 407:923–926

    CAS  PubMed  Google Scholar 

  14. Lomas DA, Mahadeva R (2002) Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest 110:1585–1590

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Chow MK, Lomas DA, Bottomley SP (2004) Promiscuous beta-strand interactions and the conformational diseases. Curr Med Chem 11:491–499

    CAS  PubMed  Google Scholar 

  16. Mast AE, Enghild JJ, Salvesen G (1991) Conformation of the reactive site loop of alpha 1-proteinase inhibitor probed by limited proteolysis. Biochemistry 31:2720–2728

    Google Scholar 

  17. Whisstock J, Bottomley S (2006) Molecular gymnastics: serpin structure, folding and misfolding. Curr Opin Struct Biol 16:761–768

    CAS  PubMed  Google Scholar 

  18. Hopkins PC, Carrell RW, Stone SR (1993) Effects of mutations in the hinge region of serpins. Biochemistry 32:7650–7657

    CAS  PubMed  Google Scholar 

  19. Naski MC, Lawrence DA, Mosher DF, Podor TJ, Ginsburg D (1993) Kinetics of inactivation of α-thrombin by plasminogen activator inhibitor-1. Comparison of the effects of native and urea-treated forms of vitronectin. J Biol Chem 268:12367–12372

    CAS  PubMed  Google Scholar 

  20. Patston PA, Church FC, Olson ST (2004) Serpin-ligand interactions. Methods 32:93–109

    CAS  PubMed  Google Scholar 

  21. Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW (1997) The anticoagulant activation of antithrombin by heparin. Proc Natl Acad Sci U S A 94:14693–14698

    Google Scholar 

  22. Olson ST, Bjork I (1991) Predominant contribution of surface approximation to the mechanism of heparin acceleration of the antithrombin-thrombin reaction. Elucidation from salt concentration effects. J Biol Chem 266:6353–6354

    CAS  PubMed  Google Scholar 

  23. Nar H, Bauer M, Stassen JM, Lang D, Gils A, Declerck PJ (2000) Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation. J Mol Biol 297:683–695

    CAS  PubMed  Google Scholar 

  24. Hekman CM, Loskutoff DJ (1985) Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 260:11581–11587

    CAS  PubMed  Google Scholar 

  25. Vaughan DE, Declerck PJ, Van Houtte E, De Mol M, Collen D (1990) Studies of recombinant plasminogen activator inhibitor- 1 in rabbits. Pharmacokinetics and evidence for reactivation of latent plasminogen activator inhibitor-1 in vivo. Circ Res 67:1281–1286

    CAS  PubMed  Google Scholar 

  26. Declerck PJ, De Mol M, Alessi MC, Baudner S, Paques E-P, Preissner KT, Muller-Berghaus G, Collen D (1988) Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. J Biol Chem 263:15454–15461

    CAS  PubMed  Google Scholar 

  27. Preissner KT, Holzhtiter S, Justus C, Muller-Berghaus G (1989) Identification and partial characterization of platelet vitronectin: evidence for complex formation with platelet-derived plasminogen activator inhibitor-1. Blood 74:1989–1996

    CAS  PubMed  Google Scholar 

  28. Seiffert D, Loskutoff DJ (1999) Kinetic analysis of the interaction between type 1 plasminogen activator inhibitor and vitronectin and evidence that the bovine inhibitor binds to a thrombin-derived amino-terminal fragment of bovine vitronectin. Biochim Biophys Acta 1078:23–30

    Google Scholar 

  29. Lawrence DA, Berkenpas MB, Palaniappan S, Ginsburg D (1994) Localization of vitronectin binding domain in plasminogen activator inhibitor-I. J Biol Chem 269:15223–15228

    CAS  PubMed  Google Scholar 

  30. Lawrence DA, Palaniappani S, Stefansson S, Olson ST, Francis-Chmura AM, Shore JD, Ginsburg D (1997) Characterization of the binding of different conformational forms of plasminogen activator inhibitor-1 to vitronectin. J Biol Chem 272:7676–7680

    CAS  PubMed  Google Scholar 

  31. Thompson LC, Goswami S, Peterson CB (2011) Metals affect the structure and activity of human plasminogen activator inhibitor-1. II. Modulation of stability and protease inhibition. Protein Sci 20:366–378

    CAS  PubMed  Google Scholar 

  32. Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geogheggan KF, Gerard RD, Goldsmith EJ (1992) Structural basis of latency in plasminogen activator inhibitor-1. Nature 355:270–273

    CAS  PubMed  Google Scholar 

  33. van Meijer M, Gebbink RK, Preissner KT, Pannekoek H (1994) Determination of the vitronectin binding site on plasminogen activator inhibitor 1 (PAI-1). FEBS Lett 352:342–346

    PubMed  Google Scholar 

  34. Boncela J, Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski CS (2001) Acute phase protein α1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity. J Biol Chem 276:35305–35311

    CAS  PubMed  Google Scholar 

  35. Smolarczyk K, Gils A, Boncela J, Declerck PJ, Cierniewski CS (2005) Function-stabilizing mechanism of plasminogen activator inhibitor type 1 induced upon binding to alpha1-acid glycoprotein. Biochemistry 44:12384–12390

    CAS  PubMed  Google Scholar 

  36. Chen SC, Henry DO, Reczek PR, Wong MK (2008) Plasminogen activator inhibitor-1 inhibits prostate tumor growth through endothelial apoptosis. Mol Cancer Ther 7:1227–1236

    CAS  PubMed  Google Scholar 

  37. Isogai C, Laug WE, Shimada H, Declerck PJ, Stins MF, Durden DL, Erdreich-Epstein A, DeClerck YA (2001) Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin. Cancer Res 61:5587–5594

    CAS  PubMed  Google Scholar 

  38. Ploplis VA, Balsara R, Sandoval-Cooper MJ, Yin ZJ, Batten J, Modi N, Gadoua D, Donahue D, Martin JA, Castellino FJ (2004) Enhanced in vitro proliferation of aortic endothelial cells from plasminogen activator inhibitor-1-deficient mice. J Biol Chem 279:6143–6151

    CAS  PubMed  Google Scholar 

  39. Soeda S, Oda M, Ochiai T, Shimeno H (2001) Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells. Mol Brain Res 91:96–103

    CAS  PubMed  Google Scholar 

  40. Degryse B, Neels JG, Czekay RP, Aertgeerts K, Kamikubo Y, Loskutoff DJ (2004) The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1. J Biol Chem 279:22595–22604

    CAS  PubMed  Google Scholar 

  41. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    CAS  PubMed  Google Scholar 

  42. Carmeliet P, Collen D (2000) Transgenic mouse models in angiogenesis and cardiovascular disease. J Pathol 190:387–405

    CAS  PubMed  Google Scholar 

  43. Uchiyama T, Kurabayashi M, Ohyama Y, Utsugi T, Akuzawa N, Sato M et al (2000) Hypoxia induces transcription of the plasminogen activator inhibitor-1 gene through genistein-sensitive tyrosine kinase pathways in vascular endothelial cells. Arterioscler Thromb Vasc Biol 20:1155–1161

    CAS  PubMed  Google Scholar 

  44. Ulisse S, Baldini E, Sorrenti S, D’Armiento M (2009) The urokinase plasminogen activator system: a target for anticancer therapy. Curr Cancer Drug Targets 9:32–71

    CAS  PubMed  Google Scholar 

  45. Bacharach E, Itin A, Keshet E (1998) Apposition-dependent induction of plasminogen activator inhibitor type 1 expression: a mechanism for balancing pericellular proteolysis during angiogenesis. Blood 92:939–945

    CAS  PubMed  Google Scholar 

  46. Pepper MS (2001) Role of matrix metalloproteinases and plasminogen activator-plasmin system in angiogenesis. Arterioscler Thromb Vasc Biol 21:1104–1107

    CAS  PubMed  Google Scholar 

  47. Simpson AJ, Booth NA, Moore NR, Bennett B (1991) Distribution of plasminogen activator inhibitor (PAI-1) in tissues. J Clin Pathol 44:139–143

    CAS  PubMed  Google Scholar 

  48. Pepper MS, Sappino AP, Stocklin R, Montesano R, Orci L, Vassalli JD (1993) Upregulation of urokinase receptor expression on migrating endothelial cells. J Cell Biol 122:673–684

    CAS  PubMed  Google Scholar 

  49. Bajou K, Noel A, Gerard RD, Masson V, Brunner N, Holst-Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, Foidart JM (1998) Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 4:923–928

    CAS  PubMed  Google Scholar 

  50. Bajou K, Masson V, Gerard RD, Schmitt PM, Albert V, Praus M, Lund LR, Frandsen TL, Brunner N, Dano K, Fusenig NE, Weidle U, Carmeliet G, Loskutoff D, Collen D, Carmeliet P, Foidart JM, Noel A (2001) The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. J Cell Biol 152:777–784

    CAS  PubMed  Google Scholar 

  51. Devy L, Blacher S, Grignet-Debrus C, Bajou K, Masson V, Gerard RD, Gils A, Carmeliet G, Carmeliet P, Declerck PJ, Noel A, Foidart JM (2002) The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J 16:147–154

    CAS  PubMed  Google Scholar 

  52. Masson V, Devy L, Grignet-Debrus C, Bernt S, Bajou K, Blacher S, Roland G, Chang Y, Fong T, Carmeliet P, Foidart JM, Noel A (2002) Mouse aortic ring assay: a new approach of the molecular genetics of angiogenesis. Biol Proced Online 4:24–31

    CAS  PubMed Central  Google Scholar 

  53. Lambert V, Munaut C, Noel A, Frankenne F, Bajou K, Gerard R, Carmeliet P, Defresne MP, Foidart JM, Rakic JM (2001) Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization. FASEB J 15:1021–1027

    CAS  PubMed  Google Scholar 

  54. Deng G, Curriden SA, Wang S, Rosenberg S, Loskutoff DJ (1996) Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J Cell Biol 134:1563–1571

    CAS  PubMed  Google Scholar 

  55. Andreasen PA, Kjoller L, Christensen L, Duffy MJ (1997) The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72:1–22

    CAS  PubMed  Google Scholar 

  56. Bajou K, Maillard C, Jost M, Lijnen HR, Gils A, Declerck P, Carmeliet P, Foidart JM, Noel A (2004) Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth. Oncogene 23:6986–6990

    CAS  PubMed  Google Scholar 

  57. Gutierrez LS, Schulman A, Brito-Robinson T, Noria F, Ploplis VA, Castellino FJ (2000) Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasmingen activator inhibitor-1. Cancer Res 60:5839–5847

    CAS  PubMed  Google Scholar 

  58. Harbeck N, Alt U, Berger U, Kates R, Kruger A, Thomssen C, Janicke F, Graeff H, Schmitt M (2000) Long term follow-up confirms prognostic impact of PAI-1 and cathepsin D and L in primary breast cancer. Int J Biol Markers 15:79–83

    CAS  PubMed  Google Scholar 

  59. Tsuchiya H, Sunayama C, Okada G, Matsuda E, Tomita K, Binder BR (1997) Plasminogen activator inhibitor-1 accelerates lung metastasis formation of human fibrosarcoma cells. Anticancer Res 17:313–316

    CAS  PubMed  Google Scholar 

  60. Stefansson S, Petitclerc E, Wong MK, McMahon GA, Brooks PC, Lawrence DA (2001) Inhibition of angiogenesis in vivo by plasminogen activator inhibitor-1. J Biol Chem 276:8135–8141

    CAS  PubMed  Google Scholar 

  61. Bacharach E, Itin A, Keshet E (1992) In vivo patterns of expression of urokinase and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis. Proc Natl Acad Sci U S A 89:10686–10690

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Bajou K, Peng H, Laug WE, Maillard C, Noel A, Foidart JM, Martial JA, DeClerck YA (2008) Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell 14:324–334

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Stack MS, Gately S, Bafetti LM, Enghild J, Soff GA (1999) Angiostatin inhibitits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. Biochem J 340:77–84

    CAS  PubMed  Google Scholar 

  64. Gately S, Twardowski P, Stack MS, Cundiff DL, Grella D, Castellino FJ, Enghild J, Kwaan HC, Lee F, Kramer RA, Volpert O, Bouck N, Soff GA (1997) The mechanism of cancer mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin. Proc Natl Acad Sci U S A 94:10868–10872

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Ramchandran R, Dhanabal M, Volk R, Waterman MJ, Segal M, Lu H, Knelbelmann B, Sukhatme VP (1999) Antiangiogenic activity of restin, NC10 domain of human collagen XV: comparison to endostatin. Biochem Biophys Res Commun 255:735–739

    CAS  PubMed  Google Scholar 

  66. Colorado PC, Torre A, Kamphaus G, Maeshima Y, Hopfer H, Takahashi K, Volk R, Zamborsky ED, Herman S, Sarkar PK, Ericksen MB, Dhanabal M, Simons M, Post M, Kufe DW, Weichselbaum RR, Sukhatme VP, Kalluri R (2000) Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res 60:2520–2526

    CAS  PubMed  Google Scholar 

  67. Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, Maeshima Y, Mier JW, Sukhatme VP, Kalluri R (2000) Canstatin, a novel matrix derived inhibitor of angiogenesis and tumor growth. J Biol Chem 275:1209–1215

    CAS  PubMed  Google Scholar 

  68. Maeshima Y, Manfredi M, Reimer C, Holthaus KA, Hopfer H, Chandamuri BR, Kharbanda S, Kalluri R (2001) Identification of the antiangiogenic site within vascular basement membrane-derived tumstatin. J Biol Chem 276:15240–15248

    CAS  PubMed  Google Scholar 

  69. O’Reilly MS, Pirie-Shepherd S, Lane WS, Folkman J (1999) Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. Science 285:1926–1928

    PubMed  Google Scholar 

  70. Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, Nakhasi H, Teruya-Feldstein J, Wirth P, Gupta G, Tosato G (1998) Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med 188:2349–2356

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Colman RW, Jameson BA, Lin Y, Johnson D, Mousa SA (2000) Domain 5 of high molecular weight kininogen (kininostatin) down-regulates endothelial cell proliferation and migration and inhibits angiogenesis. Blood 95:543–550

    CAS  PubMed  Google Scholar 

  72. Degryse B, Sier CF, Resnati M, Conese M, Blasi F (2001) PAI-1 inhibits urokinase-induced chemotaxis by internalizing the urokinase receptor. FEBS Lett 505:249–254

    CAS  PubMed  Google Scholar 

  73. McMahon GA, Petitclerc E, Stefansson S, Smith E, Wong MK, Westrick RJ, Ginsburg D, Brooks PC, Lawrence DA (2001) Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis. J Biol Chem 276:33964–33968

    CAS  PubMed  Google Scholar 

  74. Loskutoff DJ, Curriden SA, Hu G, Deng G (1999) Regulation of cell adhesion by PAI-1. APMIS 107:54–61

    CAS  PubMed  Google Scholar 

  75. Soff GA, Sanderowitz J, Gately S, Verrusio E, Weiss I, Brem S, Kwaan HC (1995) Expression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model. J Clin Invest 96:2593–2600

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Chao J, Tillman DM, Wang MY, Margolius HS, Chao L (1986) Identification of a new tissue-kallikrein binding protein. Biochem J 239:325–331

    CAS  PubMed  Google Scholar 

  77. Chao J, Chai KX, Chen LM, Xiong W, Chao S, Woodley-Miller C, Chao L (1990) Tissue kallikrein-binding protein is a serpin, I: purification, characterization, and distribution in normotensive and spontaneously hypertensive rats. J Biol Chem 265:16394–16401

    CAS  PubMed  Google Scholar 

  78. Chen LM, Ma JX, Liang YM, Chao L, Chao J (1996) Tissue kallikrein-binding protein reduces blood pressure in transgenic mice. J Biol Chem 271:27590–27594

    CAS  PubMed  Google Scholar 

  79. Chen LM, Chao L, Chao J (1997) Beneficial effects of kallikrein-binding protein in transgenic mice during endotoxic shock. Life Sci 60:1431–1436

    CAS  PubMed  Google Scholar 

  80. Chao J, Stallone JN, Liang YM, Chen LM, Chao L (1997) Kallistatin is a potent new vasodilator. J Clin Invest 100:11–17

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Wolf WC, Harley RA, Sluce D, Chao L, Chao J (1999) Localization and expression of tissue kallikrein and kallistatin in human blood vessels. J Histochem Cytochem 47:221–228

    CAS  PubMed  Google Scholar 

  82. Miao RQ, Agata J, Chao L, Chao J (2002) Kallistatin is new inhibitor of angiogenesis and tumor growth. Blood 100:3245–3252

    CAS  PubMed  Google Scholar 

  83. Miao RQ, Chen V, Chao L, Chao J (2003) Structural elements of kallistatin required for inhibition of angiogenesis. Am J Physiol Cell Physiol 284:C1604–C1613

    CAS  PubMed  Google Scholar 

  84. Suzuki K (2008) The multi-functional serpin, protein C inhibitor: beyond thrombosis and hemostasis. J Thromb Haemost 6:2017–2026

    CAS  PubMed  Google Scholar 

  85. Asanuma K, Yoshikawa T, Hayashi T, Akita N, Nakagawa N, Hamada Y, Nishioka J, Kamada H, Gabazza EC, Ido M, Uchida A, Suzuki K (2007) Protein C inhibitor inhibits breast cancer cell growth, metastasis and angiogenesis independently of its protease inhibitory activity. Int J Cancer 121:955–965

    CAS  PubMed  Google Scholar 

  86. Celerier J, Cruz A, Lamande N, Gasc JM, Corvol P (2002) Angiotensinogen and its cleaved derivatives inhibit angiogenesis. Hypertension 39:224–228

    CAS  PubMed  Google Scholar 

  87. Sheng S (2006) A role of novel serpin maspin in tumor progression: the divergence revealed through efforts to converge. J Cell Physiol 209:631–635

    CAS  PubMed  Google Scholar 

  88. Cher ML, Biliran HR Jr, Bhagat S, Meng Y, Che M, Lockett J, Abrams J, Fridman R, Zachareas M, Sheng S (2003) Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis. Proc Natl Acad Sci U S A 100:7847–7852

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Biliran H Jr, Sheng S (2001) Pleiotrophic inhibition of pericellular urokinase-type plasminogen activator system by endogenous tumor suppressive maspin. Cancer Res 61:8676–8682

    CAS  PubMed  Google Scholar 

  90. McGowen R, Biliran H Jr, Sager R, Sheng S (2000) The surface of prostate carcinoma DU145 cells mediates the inhibition of urokinase-type plasminogen activator by maspin. Cancer Res 60:4771–4778

    CAS  PubMed  Google Scholar 

  91. Frey A, Soubani AO, Adam AK, Sheng S, Pass HI, Lonardo F (2009) Nuclear, compared with combined nuclear and cytoplasmic expression of maspin, is linked in lung adenocarcinoma to reduced VEGF-A levels and in Stage I, improved survival. Histopathology 54:590–597

    PubMed Central  PubMed  Google Scholar 

  92. Cella N, Contreras A, Latha K, Rosen JM, Zhang M (2006) Maspin is associated with beta1 integrin regulating cell adhesion in mammary epithelial cells. FASEB J 20:1510–1512

    CAS  PubMed  Google Scholar 

  93. Yin S, Lockett J, Meng Y, Biliran H Jr, Blouse GE, Li X et al (2006) Maspin retards cell detachment via a novel interaction with the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system. Cancer Res 66:4173–4181

    CAS  PubMed  Google Scholar 

  94. Zhang M, Volpert O, Shi YH, Bouck N (2000) Maspin is an angiogenesis inhibitor. Nat Med 6:196–199

    PubMed  Google Scholar 

  95. Azhar A, Singh P, Rashid Q, Naseem A, Khan MS, Jairajpuri MA (2013) Antiangiogenic function of antithrombin is dependent on its conformational variation: implication for other serpins. Protein Pept Lett 20(4):403–411

    CAS  PubMed  Google Scholar 

  96. O’Reilly MS (2007) Antiangiogenic antithrombin. Semin Thromb Hemost 33:660–666

    PubMed  Google Scholar 

  97. Eaton DL, Baker JB (1993) Evidence that a variety of cultured cells secrete protease nexin and produce a distinct cytoplasmic serine protease binding factor. J Cell Physiol 117:175–182

    Google Scholar 

  98. Baker JB, Low DA, Simmer RL, Cunningham DD (1980) Protease-nexin: a cellular component that links thrombin and plasminogen activator and mediates their binding to cells. Cell 21:37–45

    CAS  PubMed  Google Scholar 

  99. Richard B et al (2004) Protease nexin-1: a cellular serpin down-regulated by thrombin in rat aortic smooth muscle cells. J Cell Physiol 201:138–145

    CAS  PubMed  Google Scholar 

  100. Bouton MC et al (2007) Protease nexin-1 interacts with thrombomodulin and modulates its anticoagulant effect. Circ Res 100:1174–1181

    CAS  PubMed  Google Scholar 

  101. Boulaftali Y et al (2010) Anticoagulant and antithrombotic properties of platelet protease nexin-1. Blood 115:97–106

    CAS  PubMed  Google Scholar 

  102. Selbonne S, Azibani F, Iatmanen S, Boulaftali Y, Richard B, Jandrot-Perrus M, Bouton MC, Arocas V (2012) In vitro and in vivo antiangiogenic properties of the serpin protease nexin-1. Mol Cell 32:496–505

    Google Scholar 

  103. Phung M, Dass CR (2006) In-vitro and in-vivo assays for angiogenesis-modulating drug discovery and development. J Pharm Pharmacol 58:153–160

    CAS  PubMed  Google Scholar 

  104. Kawaguchi T, Yamagishi SI, Sata M (2010) Structure-function relationships of PEDF. Curr Mol Med 10:302–311

    CAS  PubMed  Google Scholar 

  105. Bouck N (2002) PEDF: anti-angiogenic guardian of ocular function. Trends Mol Med 8:330–334

    CAS  PubMed  Google Scholar 

  106. Elayappan B, Ravinarayannan H, Pasha SP, Lee KJ, Gurunathan S (2009) PEDF inhibits VEGF- and EPO-induced angiogenesis in retinal endothelial cells through interruption of P13K/Akt phosphorylation. Angiogenesis 12:313–324

    CAS  PubMed  Google Scholar 

  107. Ho TC, Chen SL, Yang YC, Liao CL, Cheng HC, Tsao YP (2007) PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilican vein endothelial cells. Cardiovasc Res 76:213–223

    CAS  PubMed  Google Scholar 

  108. Yang H, Cheng R, Liu G et al (2009) PEDF inhibits growth of retinoblastoma by anti-angiogenic activity. Cancer Sci 100:2419–2425

    CAS  PubMed  Google Scholar 

  109. Cai J, Jiang WG, Grant MB, Boulton M (2006) Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor-1. J Biol Chem 281:3604–3613

    CAS  PubMed  Google Scholar 

  110. Ek ET, Dass C, Contreras KG, Choong PF (2007) Inhibition of orthotopic osteosarcoma growth and metastasis by multitargeted antitumor activities of pigment epithelium-derived factor. Clin Exp Metastasis 24:93–110

    CAS  PubMed  Google Scholar 

  111. Manalo KB, Choong PFM, Dass CR (2011) Pigment epithelium-derived factor as an impending therapeutic agent against vascular epithelial growth factor-driven tumor-angiogenesis. Mol Carcinog 50:67–72

    CAS  PubMed  Google Scholar 

  112. North S, Moenner M, Bikfalvi A (2005) Recent developments in the regulation of the angiogenic switch by cellular stress factors in tumors. Cancer Lett 218:1–14

    CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported by Projects DEC-2011/01/B/NZ3/00194 (J.B.) and DEC-2011/02/A/NZ3/00068 (C.S.C.).

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Correspondence to Joanna Boncela .

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Cierniewski, C.S., Boncela, J. (2013). Serpins in Angiogenesis. In: Dulak, J., Józkowicz, A., Łoboda, A. (eds) Angiogenesis and Vascularisation. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1428-5_5

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