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DOI: 10.1055/s-0037-1613354
Soluble Tissue Factor Interferes with Angiostatin-mediated Inhibition of Endothelial Cell Proliferation by Lysine-specific Interaction with Plasminogen Kringle Domains
Publication History
Received
22 February 2002
Accepted after resubmission
19 September 2002
Publication Date:
09 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200206/lookinside/thumbnails/10-1055-s-0037-1613354-1.jpg)
Summary
Experimental and clinical data suggest that tissue factor (TF), the major initiator of blood coagulation cascade, as well as proteases and components of the fibrinolytic system are involved in tumor growth at least in some solid tumors via effects on angiogenesis. Whereas the proand anti-angiogenic effects of the plasminogen/plasmin system and plasminogen kringle domains, respectively, are well characterized, the pathways responsible for the pro-angiogenic properties of TF remain poorly understood. To learn more about the biological significance of the recently described binding of plasminogen to the extracellular domain of TF, we examined the effects of soluble TF (sTF) on angiostatin-inhibited proliferation of endothelial cells.
In solid phase binding assays, we found that sTF binds specifically to plasminogen, to the plasminogen kringle domains K1-3, K1-5, K4, as well as to mini-plasminogen. Inhibition of binding of plasminogen and its kringle domains to sTF by the lysine analog 6-aminohexanoic acid (AHA) suggests that lysine-binding sites are involved in plasminogen interaction with TF. Moreover, in the presence of sTF, the inhibitory effect of K1-5 on bFGF-mediated HUVEC proliferation was dose-dependently and saturably abolished. This suggests that TF can interfere with the antagonistic effect of K1-5 on endothelial cell proliferation. In contrast, sTF by itself had no effect on the endothelial cell proliferation. Whereas the interference of TF with K1-5-mediated effect was prevented by AHA, this lysine analog did not abolish the proliferation inhibition of K1-5. In conclusion, the binding of sTF to the plasminogen fragment K1-5 seems to antagonize the anti-angiogenic effects of this plasminogen fragment.
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References
- 1 Callander NS, Varki N, Rao LVM. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
- 2 Sturm U, Luther T, Al-brecht S, Flössel C, Grossmann H, Müller M. Immunohistological detection of tissue factor in normal and abnormal human mammary glands using monoclonal antibodies. Virchows Archiv A Pathol Anat 1992; 42: 79-86.
- 3 Koomagi R, Volm M. Tissue-factor expression in human non-small-cell lung carcinoma measured by immunohistochemistry: correlation between tissue factor and angiogenesis. Int J Cancer 1998; 79: 19-22.
- 4 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 01: 27-31.
- 5 Abdulkadir SA, Carvalhal GF, Kaleem Z, Kisiel W, Humphrey PA, Catalona WJ, Milbrandt J. Tissue factor expression and angiogenesis in human prostate carcinoma. Hum Pathol 2000; 31: 443-7.
- 6 Takano S, Tsuboi K, Tomono Y, Mitsui Y, Nose T. Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer 2000; 82: 1967-73.
- 7 Shoji M, Hancock WW, Abe K, Micko C, Casper KA, Baine RM, Wilcox JN, Danave I, Dillehay DL, Matthews E, Contrino J, Morrissey JH, Gordon S, Edgington TS, Kudryk B, Kreutzer DL, Rickles FR. Activation of coagulation and angiogenesis in cancer: immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer. Am J Pathol 1998; 152: 399-411.
- 8 Zhang Y, Deng Y, Luther T, Müller M, Ziegler R, Waldherr R, Stern DM, Nawroth PP. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest 1994; 94: 1320-7.
- 9 Carmeliet P, Mackman N, Moons L, Luther T, Gressens P, Van Vlaenderen I, Demunck H, Kasper M, Breier G, Evrard P, Muller M, Risau W, Edgington T, Collen D. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-5.
- 10 Toomey JR, Kratzer KE, Lasky NM, Broze GJ. Effect of tissue factor deficiency on mouse and tumor development. Proc Natl Acad Sci 1997; 94: 6922-6.
- 11 Chen J, Bierhaus A, Schiekofer S, Andrassy M, Chen B, Stern DM, Nawroth PP. Tissue factor - a receptor involved in the control of cellular properties, including angiogenesis. Thromb Haemost 2001; 86: 334-45.
- 12 Carmeliet P, Collen D. Genetic analysis of blood vessel formation. Role of endothelial versus smooth muscle cells. Trends Cardiovasc Med 1997; 07: 271-81.
- 13 Kakkar AK, Chinswangwatanakul V, Lemoine NR, Tebbutt S, Williamson RC. Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma. Br J Surg 1999; 86: 890-4.
- 14 Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol 1995; 11: 73-91.
- 15 Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-61.
- 16 Plow EF, Herren T, Redlitz A, Miles L, Hoover-Plow JL. The cell biology of the plasminogen system. FASEB J 1995; 09: 939-45.
- 17 Felez J. Plasminogen binding to cell surfaces. Fibrinolysis Proteolysis 1998; 12: 183-9.
- 18 O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315-28.
- 19 Cao Y, Ji RW, Davidson D, Schaller J, Marti D, Söhndel S, McCance MS, Llinas M, Folkman J. Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells. J Biol Chem 1996; 271: 29461-67.
- 20 Ji WR, Castellino FJ, Chang Y, Deford ME, Gray H, Villarreal X, Kondri ME, Marti DN, Llinas M, Schaller J, Kramer RA, Trail PA. Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process in angiogenesis. FASEB J 1998; 12: 1731-8.
- 21 Kim JH, Kim JC, Shin SH, Chang SI, Lee HS, Chung SI. The inhibitory effect of recombinant plasminogen kringle 1–3 on the neovascularization of rabbit cornea induced by angiogenin, bFGF, and VEGF. Exp Mol Med 1999; 31: 203-9.
- 22 Moser TL, Stack MS, Asplin I, Enghild JJ, Højrup P, Everitt L, Hubchak S, Schnaper HW, Pizzo SV. Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc Natl Acad Sci 1999; 96: 2811-16.
- 23 Cao R, Wu HL, Veitonmäki N, Linden P, Farnebo J, Shi GY, Cao Y. Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. Proc Natl Acad Sci 1999; 96: 5728-33.
- 24 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. The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin. Proc Natl Acad Sci 1997; 94: 10868-72.
- 25 Falcone DJ, Khan KM, Layne T, Fernandes L. Macrophages formation of angiostatin during inflammation. A byproduct of the activation of plasminogen. J Biol Chem 1998; 273: 31480-5.
- 26 Fan Z, Larson PJ, Bognacki J, Raghu-nath PN, Tomaszewski JE, Kuo A, Canziani G, Chaiken I, Cines DB, Higazz AA. Tissue factor regulates plasminogen binding and activation. Blood 1998; 91: 1987-98.
- 27 Stone MJ, Ruf W, Miles DJ, Edgington TS, Wright PE. Recombinant soluble human tissue factor secreted by Saccharomyces cerevisiae and refolded from Escherichia coli inclusion bodies: glycosylation of mutants, activity and physical characterization. Biochem J 1995; 310: 605-14.
- 28 Magdolen V, Albrecht S, Kotzsch M, Haller C, Bürgle M, Jacob U, Großer M, Kessler H, Graeff H, Müller M, Schmitt M, Luther T. Immunological and functional analyses of the extracellular domain of human tissue factor. Biol Chem 1997; 379: 157-65.
- 29 Sottrup-Jensen L, Claeys H, Zajdel M, Petersen TE, Magnusson S. The primary structure of human plasminogen: Isolation of two lysine-binding fragments and one “mini-”plasminogen (MW 38,000) by elastase-catalyzed-specific limited proteolysis. In: Progress in Chemical Fibrinolysis and Thrombolysis. Vol.3. Davidson JF, Rowan RM, Samama MM, Desnoyers PC. eds. Raven Press; New York: 1978: 191-209.
- 30 Gonzalez-Gronow M, Gawdi G, Pizzo SV. Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells. Blood 2002; 99: 4562-7.
- 31 Lerch PG, Rickli EE, Lergier W, Gillessen D. Localization of individual lysine-binding regions in human plasminogen and investigations on their complex-forming properties. Eur J Biochem 1980; 107: 7-13.
- 32 Thewes T, Constantine K, Byeon IJ, Llinas M. Ligand interactions with the kringle 5 domain of plasminogen. A study by 1H NMR spectroscopy. J Biol Chem 1990; 265: 3906-15.
- 33 Ellis V, Behrendt N, Dano K. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor. J Biol Chem 1991; Jul 5; 266 (19) 12752-8.
- 34 Carmeliet P, Collen D. Molecular analysis of blood vessel formation and disease. Am J Physiol 1997; 273: H2091-104.
- 35 Cao Y, Chen A, An SSA, Ji RW, Davidson D, Llinas M. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J Biol Chem 1997; 272: 22924-8.
- 36 Watanabe T, Yasuda M, Yamamoto T. Angiogenesis induced by tissue factor in vitro and in vivo. Thromb Res 1999; 96: 183-9.
- 37 Randolph GJ, Luther T, Albrecht S, Magdolen V, Muller WA. Role of tissue factor in adhesion of mononuclear phagocytes to and trafficking through endothelium in vitro. Blood 1998; 92: 4167-77.
- 38 Schecter AD, Spirn B, Rossikhina M, Giesen PL, Bogdanov V, Fallon JT, Fisher EA, Schnapp LM, Nemerson Y, Taubman MB. Release of active tissue factor by human arterial smooth muscle cells. Circ Res 2000; 87: 126-32.
- 39 Kagawa H, Komiyama Y, Nakamura S, Miyake T, Miyazaki Y, Hamamoto K, Masuda M, Takahashi H, Nomura S, Fukuhara S. Expression of functional tissue factor on small vesicles of lipopolysaccharide-stimulated human vascular endothelial cells. Thromb Res 1998; 91: 297-304.
- 40 Zillmann A, Luther T, Muller I, Kotzsch M, Spannagl M, Kauke T, Oelschlagel U, Zahler S. Engelmann Platelet-associated tissue factor contributes to the collagen-triggered activation of blood coagulation. Biochem Biophys Res Commun 2001; 281: 603-9.