Tissue Factor – A Receptor Involved in the Control of Cellular Properties, Including Angiogenesis

Summary

Tissue factor (TF), the major initiator of blood coagulation, serves as a regulator of angiogenesis, tumor growth and metastasis. In several models, TF expression mediates upregulation of the proangiogenic vasular endothelial growth factor (VEGF) that can directly act on endothelial cells to promote vessel formation. This occurs through ligand binding, activation of signaling cascades, signal transduction and alteration of growth factor expression and is mediated by both, coagulation-dependent and -independent pathways. Depending on the cell type and the biological settings, TF seems to affect cellular properties through (i) factor VIIa (FVIIa)-dependent proteolysis of factor Xa (FXa) and thrombin and subsequent activation of proteinase activated receptor (PAR) -1 and PAR-2, (ii) through direct FVIIa signaling and mitogen activated protein (MAP) kinase activation, that is conferred by a not yet identified receptor, (iii) through interaction of FVII(a) proteolytic activity and signaling of the cytoplasmic domain and (iv) through cytoplasmic signaling independent of ligand binding. The role of phosphorylation of the cytoplasmic domain and the pathways controlling phosphorylation of TF remain poorly understood.

Key words

Angiogenesis - vasculogenesis - VEGF - metastasis - tumor growth

• References

• 1 Edgington TS, Mackman N, Brand K, Ruf W. The structural biology of expression and function of tissue factor. Thromb Haemost 1991; 66: 67-79.
• 2 Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost 1999; 82: 165-74.
• 3 Bach RR. Initiation of coagulation by tissue factor. CRC Crit Rev Biochem 1988; 23: 339-68.
• 4 Broze Jr GJ. Binding of human factor VII and VIIa to monocytes. J Clin Invest 1982; 70: 526-35.
• 5 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134: 1087-97.
• 6 Nemerson Y, Giesen PL. Some thoughts about localization and expression of tissue factor. Blood Coagul Fibrinolysis 1998; 9 (Suppl. 01) S45-7.
• 7 Rao LV, Pendurthi UR. Tissue factor on cells. Blood Coagul Fibrinolysis 1998; 9 (Suppl. 01) S27-35.
• 8 Muller M, Flossel C, Haase M, Luther T, Albrecht S, Nawroth PP. et al. Cellular localization of tissue factor in human breast cancer cell lines. Virchows Arch B Cell Pathol Incl Mol Pathol 1993; 64: 265-9.
• 9 Preissner KT, Nawroth PP, Kanse SM. Vascular protease receptors: integrating haemostasis and endothelial cell functions. J Pathol 2000; 190: 360-72.
• 10 Prydz H, Camerer E, Rottingen JA, Wiiger MT, Gjernes E. Cellular consequences of the initiation of blood coagulation. Thromb Haemost 1999; 82: 183-92.
• 11 Camerer E, Kolsto AB, Prydz H. Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res 1996; 81: 1-41.
• 12 Almendral JM, Sommer D, Macdonald-Bravo H, Burckhardt J, Perera J, Bravo R. Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol 1988; 8: 2140-8.
• 13 Hartzell S, Ryder K, Lanahan A, Lau LF, Nathan D. A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homo-logous to human tissue factor. Mol Cell Biol 1989; 9: 2567-73.
• 14 Tenno T, Botling J, Oberg F, Nilsson K, Siegbahn A. Tissue factor expression in human monocytic cell lines. Thromb Res 1997; 88: 215-28.
• 15 van den Eijnden MM, Steenhauer SI, Reitsma PH, Bertina RM. Tissue factor expression during monocyte-macrophage differentiation. Thromb Haemost 1997; 77: 1129-36.
• 16 Bierhaus A, Chen J, Liliensiek B, Nawroth PP. LPS and cytokine-activated endothelium. Semin Thromb Hemost 2000; 26: 571-87.
• 17 Collins PW, Noble KE, Reittie JR, Hoffbrand AV, Pasi KJ, Yong KL. Induction of tissue factor expression in human monocyte/endothelium cocultures. Br J Haematol 1995; 91: 963-70.
• 18 Bevilacqua MP, Nelson RM. Endothelial-leukocyte adhesion molecules in inflammation and metastasis. Thromb Haemost 1993; 70: 152-4.
• 19 Edgington TS, Mackman N, Fan ST, Ruf W. Cellular immune and cytokine pathways resulting in tissue factor expression and relevance to septic shock. Nouv Rev Fr Hematol 1992; 34 suppl S15-27.
• 20 Drake TA, Pang M. Effects of interleukin-1, lipopolysaccharide, and streptococci on procoagulant activity of cultured human cardiac valve endothelial and stromal cells. Infect Immun 1989; 57: 507-12.
• 21 Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med 1986; 163: 1363-75.
• 22 Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740-5.
• 23 Nawroth PP, Handley DA, Esmon CT, Stern DM. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 1986; 83: 3460-4.
• 24 Stern DM, Bank I, Nawroth PP, Cassimeris J, Kisiel W, Fenton JW II. et al. Self-regulation of procoagulant events on the endothelial cell surface. J Exp Med 1985; 162: 1223-35.
• 25 Bierhaus A, Zhang Y, Deng Y, Mackman N, Quehenberger P, Haase M. et al. Mechanism of the tumor necrosis factor alpha-mediated induction of endothelial tissue factor. J Biol Chem 1995; 270: 26419-32.
• 26 Bierhaus A, Hemmer CJ, Mackman N, Kutob R, Ziegler R, Dietrich M. et al. Antiparasitic treatment of patients with P. falciparum malaria reduces the ability of patient serum to induce tissue factor by decreasing NF-kappa B activation. Thromb Haemost 1995; 73: 39-48.
• 27 Corseaux D, Meurice T, Six I, Rugeri L, Ezekowitz MD, Rouvier P. et al. Basic fibroblast growth factor increases tissue factor expression in circulating monocytes and in vascular wall. Circulation 2000; 101: 2000-6.
• 28 Ernofsson M, Siegbahn A. Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor. Thromb Res 1996; 83: 307-20.
• 29 Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC. et al. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990; 172: 1535-45.
• 30 Franco RF, de Jonge E, Dekkers PE, Timmerman JJ, Spek CA, van Deventer SJ. et al. The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation. Blood 2000; 96: 554-9.
• 31 Erlich J, Fearns C, Mathison J, Ulevitch RJ, Mackman N. Lipopolysaccharide induction of tissue factor expression in rabbits. Infect Immun 1999; 67: 2540-6.
• 32 Bohrer H, Qiu F, Zimmermann T, Zhang Y, Jllmer T, Mannel D. et al. Role of NFkappaB in the mortality of sepsis. J Clin Invest 1997; 100: 972-85.
• 33 Mackman N, Sawdey MS, Keeton MR, Loskutoff DJ. Murine tissue factor gene expression in vivo. Tissue and cell specificity and regulation by lipopolysaccharide. Am J Pathol 1993; 143: 76-84.
• 34 Semeraro N, Triggiani R, Montemurro P, Cavallo LG, Colucci M. Enhanced endothelial tissue factor but normal thrombomodulin in endotoxin-treated rabbits. Thromb Res 1993; 71: 479-86.
• 35 Brand K, Fowler BJ, Edgington TS, Mackman N. Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and post-transcriptional levels in response to lipopolysaccharide. Mol Cell Biol 1991; 11: 4732-8.
• 36 Drake TA, Ruf W, Morrissey JH, Edgington TS. Functional tissue factor is entirely cell surface expressed on lipopolysaccharide-stimulated human blood monocytes and a constitutively tissue factor-producing neoplastic cell line. J Cell Biol 1989; 109: 389-95.
• 37 Colucci M, Balconi G, Lorenzet R, Pietra A, Locati D, Donati MB. et al. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-6.
• 38 Mackman N, Brand K, Edgington TS. Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites. J Exp Med 1991; 174: 1517-26.
• 39 Ichikawa K, Yoshinari M, Iwase M, Wakisaka M, Doi Y, Iino K. et al. Advanced glycosylation end products induced tissue factor expression in human monocyte-like U937 cells and increased tissue factor expression in monocytes from diabetic patients. Atherosclerosis 1998; 136: 281-7.
• 40 Bierhaus A, Illmer T, Kasper M, Luther T, Quehenberger P, Tritschler H. et al. Advanced glycation end product (AGE)-mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE. Circulation 1997; 96: 2262-71.
• 41 Cui MZ, Penn MS, Chisolm GM. Native and oxidized low density lipoprotein induction of tissue factor gene expression in smooth muscle cells is mediated by both Egr-1 and Sp1. J Biol Chem 1999; 274: 32795-802.
• 42 Drake TA, Hannani K, Fei HH, Lavi S, Berliner JA. Minimally oxidized low-density lipoprotein induces tissue factor expression in cultured human endothelial cells. Am J Pathol 1991; 138: 601-7.
• 43 Yan SF, Fujita T, Lu J, Okada K, Shan Zou Y, Mackman N. et al. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med 2000; 6: 1355-61.
• 44 Yan SF, Pinsky DJ, Stern DM. A pathway leading to hypoxia-induced vascular fibrin deposition. Semin Thromb Hemost 2000; 26: 479-83.
• 45 Yan SF, Zou YS, Gao Y, Zhai C, Mackman N, Lee SL. et al. Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia. Proc Natl Acad Sci USA 1998; 95: 8298-303.
• 46 Yan SF, Mackman N, Kisiel W, Stern DM, Pinsky DJ. Hypoxia/Hypoxemia-induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis. Arterioscler Thromb Vasc Biol 1999; 19: 2029-35.
• 47 Mackman N. Regulation of the tissue factor gene. Thromb Haemost 1997; 78: 747-54.
• 48 Mackman N. Regulation of the tissue factor gene. FASEB J 1995; 9: 883-9.
• 49 Liu SL, Rand A, Kelm Jr RJ, Getz MJ. The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts. Oncogene 2000; 19: 3352-62.
• 50 Holzmuller H, Moll T, Hofer-Warbinek R, Mechtcheriakova D, Binder BR, Hofer E. A transcriptional repressor of the tissue factor gene in endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 1804-11.
• 51 Mackman N. Lipopolysaccharide induction of gene expression in human monocytic cells. Immunol Res 2000; 21: 247-51.
• 52 Armstead VE, Opentanova IL, Minchenko AG, Lefer AM. Tissue factor expression in vital organs during murine traumatic shock: role of transcription factors AP-1 and NF-kappaB. Anesthesiology 1999; 91: 1844-52.
• 53 Hall AJ, Vos HL, Bertina RM. Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor kappaB nuclear translocation. J Biol Chem 1999; 274: 376-83.
• 54 Osterud B. Tissue factor expression by monocytes: regulation and patho-physiological roles. Blood Coagul Fibrinolysis 1998; 9 (Suppl. 01) S9-14.
• 55 Shi RJ, Simpson-Haidaris PJ, Lerner NB, Marder VJ, Silverman DJ, Sporn LA. Transcriptional regulation of endothelial cell tissue factor expression during Rickettsia rickettsii infection: involvement of the transcription factor NF-kappaB. Infect Immun 1998; 66: 1070-5.
• 56 Holschermann H, Terhalle HM, Zakel U, Maus U, Parviz B, Tillmanns H. et al. Monocyte tissue factor expression is enhanced in women who smoke and use oral contraceptives. Thromb Haemost 1999; 82: 1614-20.
• 57 Bierhaus A, Zhang Y, Quehenberger P, Luther T, Haase M, Muller M. et al. The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B. Thromb Haemost 1997; 77: 772-82.
• 58 Pendurthi UR, Williams JT, Rao LV. Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. Arterioscler Thromb Vasc Biol 1997; 17: 3406-13.
• 59 Oeth P, Parry GC, Mackman N. Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NF-kappa B/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression. Arterioscler Thromb Vasc Biol 1997; 17: 365-74.
• 60 Moll T, Czyz M, Holzmuller H, Hofer-Warbinek R, Wagner E, Winkler H. et al. Regulation of the tissue factor promoter in endothelial cells. Binding of NF kappa B-, AP-1-, and Sp1-like transcription factors. J Biol Chem 1995; 270: 3849-57.
• 61 Felts SJ, Stoflet ES, Eggers CT, Getz MJ. Tissue factor gene transcription in serum-stimulated fibroblasts is mediated by recruitment of c-Fos into specific AP-1 DNA-binding complexes. Biochemistry 1995; 34: 12355-62.
• 62 Holschermann H, Kohl O, Maus U, Durfeld F, Bierhaus A, Nawroth PP. et al. Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients. Circulation 1997; 96: 4232-8.
• 63 Mechtcheriakova D, Schabbauer G, Lucerna M, Clauss M, De Martin R, Binder BR. et al. Specificity, diversity, and convergence in VEGF and TNF-(alpha) signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells. FASEB J 2001; 15: 230-42.
• 64 Groupp ER, Donovan-Peluso M. Lipopolysaccharide induction of THP-1 cells activates binding of c-Jun, Ets, and Egr-1 to the tissue factor promoter. J Biol Chem 1996; 271: 12423-30.
• 65 Cui MZ, Parry GC, Oeth P, Larson H, Smith M, Huang RP. et al. Transcriptional regulation of the tissue factor gene in human epithelial cells is mediated by Sp1 and EGR-1. J Biol Chem 1996; 271: 2731-9.
• 66 Krikun G, Schatz F, Mackman N, Guller S, Demopoulos R, Lockwood CJ. Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3. Mol Endocrinol 2000; 14: 393-400.
• 67 Mechtcheriakova D, Wlachos A, Holzmuller H, Binder BR, Hofer E. Vascular endothelial cell growth factor-induced tissue factor expression in endothelial cells is mediated by EGR-1. Blood 1999; 93: 3811-23.
• 68 Armesilla AL, Lorenzo E, Gomez del Arco P, Martinez-Martinez S, Alfranca A, Redondo JM. Vascular endothelial growth factor activates nuclear factor of activated T cells in human endothelial cells: a role for tissue factor gene expression. Mol Cell Biol 1999; 19: 2032-43.
• 69 Xuereb JM, Sie P, Boneu B, Constans J. Inhibition of tissue factor synthesis by disruption of ERK kinases and PKC signaling pathways in human vascular SMCs. Thromb Haemost 2000; 84: 129-36.
• 70 Wiiger MT, Pringle S, Pettersen KS, Narahara N, Prydz H. Effects of binding of ligand (FVIIa) to induced tissue factor in human endothelial cells. Thromb Res 2000; 98: 311-21.
• 71 Røttingen J-A, Enden T, Camerer E, Iversen J-G, Prydz H. Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor. J Biol Chem 1995; 270: 4650-60.
• 72 Camerer E, Røttingen J-A, Iversen J-G, Prydz H. Coagulation factors VII and X induce Ca2+ oscillations in Madin-Darby canine kidney cells only when proteolytically active. J Biol Chem 1996; 271: 29034-42.
• 73 Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA 1990; 87: 6934-8.
• 74 Ishibashi H, Nakagawa K, Onimaru M, Castellanous EJ, Kaneda Y, Nakashima Y. et al. Sp1 decoy transfected to carcinoma cells suppresses the expression of vascular endothelial growth factor, transforming growth factor beta1, and tissue factor and also cell growth and invasion activities. Cancer Res 2000; 60: 6531-6.
• 75 Hsu TC, Young MR, Cmarik J, Colburn NH. Activator protein 1 (AP-1)-and nuclear factor kappaB (NF-kappaB)-dependent transcriptional events in carcinogenesis. Free Radic Biol Med 2000; 28: 1338-48.
• 76 Pawar S, Kartha S, Toback FG. Differential gene expression in migrating renal epithelial cells after wounding. J Cell Physiol 1995; 165: 556-65.
• 77 Ishii H, Takada K, Higuchi T, Sugiyama J. Verotoxin-1 induces tissue factor expression in human umbilical vein endothelial cells through activation of NF-kappaB/Rel and AP-1. Thromb Haemost 2000; 84: 712-21.
• 78 Parry GC, Mackman N. Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol 1995; 15: 612-21.
• 79 Cooper JT, Stroka DM, Brostjan C, Palmetshofer A, Bach FH, Ferran C. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. J Biol Chem 1996; 271: 18068-73.
• 80 Dechend R, Maass M, Gieffers J, Dietz R, Scheidereit C, Leutz A. et al. Chlamydia pneumoniae infection of vascular smooth muscle and endothelial cells activates NF-kappaB and induces tissue factor and PAI-1 expression: a potential link to accelerated arteriosclerosis. Circulation 1999; 100: 1369-73.
• 81 Sahni SK, Turpin LC, Brown TL, Sporn LA. Involvement of protein kinase C in Rickettsia rickettsii-induced transcriptional activation of the host endothelial cell. Infect Immun 1999; 67: 6418-23.
• 82 Pal S, Datta K, Khosravi-Far R, Mukhopadhyay D. Role of PKC z in Ras-mediated transcriptional activation of vascular permeability factor/vascular endothelial growth factor expression. J Biol Chem 2001; 276: 2395-403.
• 83 Tanaka T, Kanai H, Sekiguchi K, Aihara Y, Yokoyama T, Arai M. et al. Induction of VEGF Gene Transcription by IL-1 beta is Mediated Through Stress-activated MAP Kinases and Sp1 Sites in Cardiac Myocytes. J Mol Cell Cardiol 2000; 32: 1955-67.
• 84 Finkenzeller G, Sparacio A, Technau A, Marme D, Siemeister G. Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression. Oncogene 1997; 15: 669-76.
• 85 Milanini J, Vinals F, Pouyssegur J, Pages G. p42/p44 MAP kinase module plays a key role in the transcriptional regulation of the vascular endothelial growth factor gene in fibroblasts. J Biol Chem 1998; 273: 18165-72.
• 86 Pal S, Claffey KP, Cohen HT, Mukhopadhyay D. Activation of Sp1-mediated vascular permeability factor/vascular endothelial growth factor transcription requires specific interaction with protein kinase C zeta. J Biol Chem 1998; 273: 26277-80.
• 87 Ryuto M, Ono M, Izumi H, Yoshida S, Weich HA, Kohno K. et al. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1. J Biol Chem 1996; 271: 28220-8.
• 88 Matsushita K, Motani R, Sakuta T, Nagaoka S, Matsuyama T, Abeyama K. et al. Lipopolysaccharide enhances the production of vascular endothelial growth factor by human pulp cells in culture. Infect Immun 1999; 67: 1633-9.
• 89 Chua CC, Hamdy RC, Chua BH. Mechanism of transforming growth factor-beta1-induced expression of vascular endothelial growth factor in murine osteoblastic MC3T3-E1 cells. Biochim Biophys Acta 2000; 1497: 69-76.
• 90 Diaz BV, Lenoir MC, Ladoux A, Frelin C, Demarchez M, Michel S. Regulation of vascular endothelial growth factor expression in human keratinocytes by retinoids. J Biol Chem 2000; 275: 642-50.
• 91 Hossain MA, Bouton CM, Pevsner J, Laterra J. Induction of vascular endothelial growth factor in human astrocytes by lead. Involvement of a protein kinase C/activator protein-1 complex-dependent and hypoxiainducible factor 1-independent signaling pathway. J Biol Chem 2000; 275: 27874-82.
• 92 Damert A, Ikeda E, Risau W. Activator-protein-1 binding potentiates the hypoxia-induciblefactor-1-mediated hypoxia-induced transcriptional activation of vascular-endothelial growth factor expression in C6 glioma cells. Biochem J 1997; 327 Pt 2 419-23.
• 93 Mori K, Tani M, Kamata K, Kawamura H, Urata Y, Goto S. et al. Mitogen-activated protein kinase, ERK1/2, is essential for the induction of vascular endothelial growth factor by ionizing radiation mediated by activator protein-1 in human glioblastoma cells. Free Radic Res 2000; 33: 157-66.
• 94 Abeyama K, Eng W, Jester JV, Vink AA, Edelbaum D, Cockerell CJ. et al. A role for NF-kappaB-dependent gene transactivation in sunburn. J Clin Invest 2000; 105: 1751-9.
• 95 Camerer E, Gjernes E, Wiiger M, Pringle S, Prydz H. Binding of factor VIIa to tissue factor on keratinocytes induces gene expression. J Biol Chem 2000; 275: 6580-5.
• 96 Carmeliet P, Moons L, Dewerchin M, Mackman N, Luther T, Breier G. et al. Insights in vessel development and vascular disorders using targeted inactivation and transfer of vascular endothelial growth factor, the tissue factor receptor, and the plasminogen system. Ann N Y Acad Sci 1997; 811: 191-206.
• 97 Shoji M, Hancock WW, Abe K, Micko C, Casper KA, Baine RM. et al. 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.
• 98 Luther T, Flossel C, Mackman N, Bierhaus A, Kasper M, Albrecht S. et al. Tissue factor expression during human and mouse development. Am J Pathol 1996; 149: 101-13.
• 99 Ong K, Horsfall W, Conway EM, Schuh AC. Early embryonic expression of murine coagulation system components. Thromb Haemost 2000; 84: 1023-30.
• 100 Carmeliet P, Mackman N, Moons L, Luther T, Gressens P, Van Vlaenderen I. et al. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-5.
• 101 Bugge TH, Xiao Q, Kombrinck KW, Flick MJ, Holmback K, Danton MJ. et al. Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc Natl Acad Sci USA 1996; 93: 6258-63.
• 102 Toomey JR, Kratzer KE, Lasky NM, Stanton JJ, Broze Jr GJ. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 1996; 88: 1583-7.
• 103 Suh TT, Holmback K, Jensen NJ, Daugherty CC, Small K, Simon DI. et al. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev 1995; 9: 2020-33.
• 104 Parry GC, Mackman N. Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain. J Clin Invest 2000; 105: 1547-54.
• 105 Parry GC, Erlich JH, Carmeliet P, Luther T, Mackman N. Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest 1998; 101: 560-9.
• 106 Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M. et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435-9.
• 107 Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS. et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439-42.
• 108 Erlich J, Parry GC, Fearns C, Muller M, Carmeliet P, Luther T. et al. Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation. Proc Natl Acad Sci USA 1999; 96: 8138-43.
• 109 Ruf W, Mueller BM. Tissue factor signaling. Thromb Haemost 1999; 82: 175-82.
• 110 Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140: 1241-53.
• 111 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.
• 112 Xuereb JM, Sie P, Boneu B, Constans J. Up-regulation of tissue factor expression by platelet-derived growth factor in human vascular smooth muscle cells in culture – role of mitogen-activated protein kinase and effects of intracellular cyclic AMP. Thromb Haemost 1997; 78: 1520-6.
• 113 Gorlach A, Brandes RP, Bassus S, Kronemann N, Kirchmaier CM, Busse R. et al. Oxidative stress and expression of p22phox are involved in the up-regulation of tissue factor in vascular smooth muscle cells in response to activated platelets. FASEB J 2000; 14: 1518-28.
• 114 Nawroth P, Handley D, Matsueda G, De Waal R, Gerlach H, Blohm D. et al. Tumor necrosis factor/cachectin-induced intravascular fibrin formation in meth A fibrosarcomas. J Exp Med 1988; 168: 637-47.
• 115 Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249-57.
• 116 Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146: 1029-39.
• 117 Senger DR, Brown LF, Claffey KP, Dvorak HF. Vascular permeability factor, tumor angiogenesis and stroma generation. Invasion Metastasis 1995; 14: 385-94.
• 118 Martin P. Wound healing – aiming for perfect skin regeneration. Science 1997; 276: 75-81.
• 119 Pendurthi UR, Allen KE, Ezban M, Rao LV. Factor VIIa and thrombin induce the expression of Cyr61 and connective tissue growth factor, extracellular matrix signaling proteins that could act as possible downstream mediators in factor VIIa x tissue factor-induced signal transduction. J Biol Chem 2000; 275: 14632-41.
• 120 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.
• 121 Abe K, Shoji M, Chen J, Bierhaus A, Danave I, Micko C. et al. Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci USA 1999; 96: 8663-8.
• 122 Zhang Y, Deng Y, Luther T, Muller M, Ziegler R, Waldherr R. et al. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest 1994; 94: 1320-7.
• 123 Clauss M, Grell M, Fangmann C, Fiers W, Scheurich P, Risau W. Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: functional analysis of the tumor necrosis factor receptors. FEBS Lett 1996; 390: 334-8.
• 124 Nakagawa K, Zhang Y, Tsuji H, Yoshizumi M, Kasahara T, Nishimura H. et al. The angiogenic effect of tissue factor on tumors and wounds. Semin Thromb Hemost 1998; 24: 207-10.
• 125 Li W, Keller G. VEGF nuclear accumulation correlates with phenotypical changes in endothelial cells. J Cell Sci 2000; 113: 1525-34.
• 126 Sato Y, Asada Y, Marutsuka K, Hatakeyama K, Sumiyoshi A. Tissue factor induces migration of cultured aortic smooth muscle cells. Thromb Haemost 1996; 75: 389-92.
• 127 Taniguchi T, Kakkar AK, Tuddenham EG, Williamson RC, Lemoine NR. Enhanced expression of urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. Cancer Res 1998; 58: 4461-7.
• 128 Siegbahn A, Johnell M, Rorsman C, Ezban M, Heldin CH, Ronnstrand L. Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemo-taxis. Blood 2000; 96: 3452-8.
• 129 Hasenstab D, Lea H, Hart CE, Lok S, Clowes AW. Tissue factor over-expression in rat arterial neointima models thrombosis and progression of advanced atherosclerosis. Circulation 2000; 101: 2651-7.
• 130 Camerer E, Pringle S, Skartlien AH, Wiiger M, Prydz K, Kolsto AB. et al. Opposite sorting of tissue factor in human umbilical vein endothelial cells and Madin-Darby canine kidney epithelial cells. Blood 1996; 88: 1339-49.
• 131 Narahara N, Enden T, Wiiger M, Prydz H. Polar expression of tissue factor in human umbilical vein endothelial cells. Arterioscler Thromb 1994; 14: 1815-20.
• 132 Muller M, Albrecht S, Golfert F, Hofer A, Funk RH, Magdolen V. et al. Localization of tissue factor in actin-filament-rich membrane areas of epithelial cells. Exp Cell Res 1999; 248: 136-47.
• 133 Luther T, Dittert DD, Kotzsch M, Erlich J, Albrecht S, Mackman N. et al. Functional implications of tissue factor localization to cell-cell contacts in myocardium. J Pathol 2000; 192: 121-30.
• 134 Nawroth PP, Stern DM, Kisiel W, Bach R. Cellular requirements for tissue factor generation by bovine aortic endothelial cells in culture. Thromb Res 1985; 40: 677-91.
• 135 Bromberg ME, Sundaram R, Homer RJ, Garen A, Konigsberg WH. Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost 1999; 82: 88-92.
• 136 Mueller BM, Ruf W. Requirement for binding of catalytically active factor VIIa in tissue factor-dependent experimental metastasis. J Clin Invest 1998; 101: 1372-8.
• 137 Ruf W, Mueller BM. Tissue factor in cancer angiogenesis and metastasis. Curr Opin Hematol 1996; 3: 379-84.
• 138 Rickles FR, Hair GA, Zeff RA, Lee E, Bona RD. Tissue factor expression in human leukocytes and tumor cells. Thromb Haemost 1995; 74: 391-5.
• 139 Rao LV. Tissue factor as a tumor procoagulant. Cancer Metastasis Rev 1992; 11: 249-66.
• 140 Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
• 141 Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RC. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82: 1101-4.
• 142 Hamada K, Kuratsu J, Saitoh Y, Takeshima H, Nishi T, Ushio Y. Expression of tissue factor correlates with grade of malignancy in human glioma. Cancer 1996; 77: 1877-83.
• 143 Abdulkadir SA, Carvalhal GF, Kaleem Z, Kisiel W, Humphrey PA, Catalona WJ. et al. Tissue factor expression and angiogenesis in human prostate carcinoma. Hum Pathol 2000; 31: 443-7.
• 144 Sturm U, Luther T, Albrecht S, Flossel C, Grossmann H, Muller M. Immunohistological detection of tissue factor in normal and abnormal human mammary glands using monoclonal antibodies. Virchows Arch A Pathol Anat Histopathol 1992; 421: 79-86.
• 145 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.
• 146 Lwaleed BA, Chisholm M, Francis JL. Urinary tissue factor levels in patients with breast and colorectal cancer. J Pathol 1999; 187: 291-4.
• 147 Seto S, Onodera H, Kaido T, Yoshikawa A, Ishigami S, Arii S. et al. Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis. Cancer 2000; 88: 295-301.
• 148 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.
• 149 Ogiichi T, Hirashima Y, Nakamura S, Endo S, Kurimoto M, Takaku A. Tissue factor and cancer procoagulant expressed by glioma cells participate in their thrombin-mediated proliferation. J Neurooncol 2000; 46: 1-9.
• 150 Luther T, Flossel C, Albrecht S, Kotzsch M, Muller M. Tissue factor expression in normal and abnormal mammary gland. Nat Med 1996; 2: 491-2.
• 151 Vrana JA, Stang MT, Grande JP, Getz MJ. Expression of tissue factor in tumor stroma correlates with progression to invasive human breast cancer: paracrine regulation by carcinoma cell-derived members of the transforming growth factor beta family. Cancer Res 1996; 56: 5063-70.
• 152 Contrino J, Hair G, Kreutzer DL, Rickles FR. In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant pheno-type of human breast disease. Nat Med 1996; 2: 209-15.
• 153 Nishi T, Goto T, Takeshima H, Hamada K, Tada K, Saito Y. et al. Tissue factor expressed in pituitary adenoma cells contributes to the development of vascular events in pituitary adenomas. Cancer 1999; 86: 1354-61.
• 154 Toomey JR, Kratzer KE, Lasky NM, Broze Jr GJ. Effect of tissue factor deficiency on mouse and tumor development. Proc Natl Acad Sci USA 1997; 94: 6922-6.
• 155 Fan Z, Larson PJ, Bognacki J, Raghunath PN, Tomaszewski JE, Kuo A. et al. Tissue factor regulates plasminogen binding and activation. Blood 1998; 91: 1987-98.
• 156 Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86: 353-64.
• 157 Verheul HM, Hoekman K, Luykx-de Bakker S, Eekman CA, Folman CC, Broxterman HJ. et al. Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 1997; 3: 2187-90.
• 158 Haralabopoulos GC, Grant DS, Kleinman HK, Maragoudakis ME. Thrombin promotes endothelial cell alignment in Matrigel in vitro and angio-genesis in vivo. Am J Physiol 1997; 273: C239-45.
• 159 Chiarugi V, Ruggiero M, Magnelli L. Molecular polarity in endothelial cells and tumor-induced angiogenesis. Oncol Res 2000; 12: 1-4.
• 160 Shigemori C, Wada H, Matsumoto K, Shiku H, Nakamura S, Suzuki H. Tissue factor expression and metastatic potential of colorectal cancer. Thromb Haemost 1998; 80: 894-8.
• 161 Sawada M, Miyake S, Ohdama S, Matsubara O, Masuda S, Yakumaru K. et al. Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis. Br J Cancer 1999; 79: 472-7.
• 162 Ueno T, Toi M, Koike M, Nakamura S, Tominaga T. Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration. Br J Cancer 2000; 83: 164-70.
• 163 Esumi N, Fan D, Fidler IJ. Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor. Cancer Res 1991; 51: 4549-56.
• 164 Fischer EG, Ruf W, Mueller BM. Tissue factor-initiated thrombin generation activates the signaling thrombin receptor on malignant melanoma cells. Cancer Res 1995; 55: 1629-32.
• 165 Bromberg ME, Konigsberg WH, Madison JF, Pawashe A, Garen A. Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proc Natl Acad Sci USA 1995; 92: 8205-9.
• 166 Hu Z, Sun Y, Garen A. Targeting tumor vasculature endothelial cells and tumor cells for immunotherapy of human melanoma in a mouse xenograft model. Proc Natl Acad Sci USA 1999; 96: 8161-6.
• 167 Zhang Y, Deng Y, Wendt T, Liliensiek B, Bierhaus A, Greten J. et al. Intravenous somatic gene transfer with antisense tissue factor restores blood flow by reducing tumor necrosis factor-induced tissue factor expression and fibrin deposition in mouse meth-A sarcoma. J Clin Invest 1996; 97: 2213-24.
• 168 Thorpe PE, Ran S. Tumor infarction by targeting tissue factor to tumor vasculature. Cancer J Sci Am 2000; 6 (Suppl. 03) S237-44.
• 169 Mannel DN, Echtenacher B. TNF in the inflammatory response. Chem Immunol 2000; 74: 141-61.
• 170 Hamon Y, Broccardo C, Chambenoit O, Luciani MF, Toti F, Chaslin S. et al. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2000; 2: 399-406.
• 171 Greeno EW, Bach RR, Moldow CF. Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest 1996; 75: 281-9.
• 172 Taubman MB, Giesen PL, Schecter AD, Nemerson Y. Regulation of the procoagulant response to arterial injury. Thromb Haemost 1999; 82: 801-5.
• 173 Ryan J, Brett J, Tijburg P, Bach RR, Kisiel W, Stern D. Tumor necrosis factor-induced endothelial tissue factor is associated with subendothelial matrix vesicles but is not expressed on the apical surface. Blood 1992; 80: 966-74.
• 174 Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-3.
• 175 Ollivier V, Bentolila S, Chabbat J, Hakim J, de Prost D. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII. Blood 1998; 91: 2698-703.
• 176 Ollivier V, Chabbat J, Herbert JM, Hakim J, de Prost D. Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves thrombin and factor Xa. Arterioscler Thromb Vasc Biol 2000; 20: 1374-81.
• 177 Camerer E, Huang W, Coughlin SR. Tissue facor and factor X dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000; 97: 5255-60.
• 178 Sorensen BB, Freskgard PO, Nielsen LS, Rao LV, Ezban M, Petersen LC. Factor VIIa-induced p44/42 mitogen-activated protein kinase activation requires the proteolytic activity of factor VIIa and is independent of the tissue factor cytoplasmic domain. J Biol Chem 1999; 274: 21349-54.
• 179 Masuda M, Nakamura S, Murakami T, Komiyama Y, Takahashi H. Association of tissue factor with a gamma chain homodimer of the IgE receptor type I in cultured human monocytes. Eur J Immunol 1996; 26: 2529-32.
• 180 Poulsen LK, Jacobsen N, Sorensen BB, Bergenhem NC, Kelly JD, Foster DC. et al. Signal transduction via the mitogen-activated protein kinase pathway induced by binding of coagulation factor VIIa to tissue factor. J Biol Chem 1998; 273: 6228-32.
• 181 Petersen LC, Thastrup O, Hagel G, Sorensen BB, Freskgard PO, Rao LV. et al. Exclusion of known protease-activated receptors in factor VIIa-induced signal transduction. Thromb Haemost 2000; 83: 571-6.
• 182 Prydz H. A new paradigm for blood coagulation research. Thromb Haemost 2000; 83: 520-2.
• 183 Camerer E, Rottingen JA, Gjernes E, Larsen K, Skartlien AH, Iversen JG. et al. Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene. J Biol Chem 1999; 274: 32225-33.
• 184 Zioncheck TF, Roy S, Vehar GA. The cytoplasmic domain of tissue factor is phosphorylated by a protein kinase C-dependent mechanism. J Biol Chem 1992; 267: 3561-4.
• 185 Mody RS, Carson SD. Tissue factor cytoplasmic domain peptide is multiply phosphorylated in vitro. Biochemistry 1997; 36: 7869-75.
• 186 Car BD, Slauson DO, Dore M, Suyemoto MM. Endotoxin-mediated bovine alveolar macrophage procoagulant induction is dependent on protein kinase C activation. Inflammation 1990; 14: 681-9.
• 187 Herbert JM, Savi P, Laplace MC, Dumas A, Dol F. Chelerythrine, a selective protein kinase C inhibitor, counteracts pyrogen-induced expression of tissue factor without effect on thrombomodulin down-regulation in endothelial cells. Thromb Res 1993; 15: 487-3.
• 188 Taubman MB, Marmur JD, Rosenfield CL, Guha A, Nichtberger S, Nemerson Y. Agonist-mediated tissue factor expression in cultured vascular smooth muscle cells. Role of Ca2+ mobilization and protein kinase C activation. J Clin Invest 1993; 91: 547-52.
• 189 Neuenschwander PF, Morrissey JH. Deletion of the membrane anchoring region of tissue factor abolishes autoactivation of factor VII but not cofactor function. Analysis of a mutant with a selective deficiency in activity. J Biol Chem 1992; 267: 14477-82.
• 190 Kunzelmann-Marche C, Satta N, Toti F, Zhang Y, Nawroth PP, Morrissey JH. et al. The influence exerted by a restricted phospholipid microenvironment on the expression of tissue factor activity at the cell plasma membrane surface. Thromb Haemost 2000; 83: 282-9.
• 191 Watanabe T, Yasuda M, Yamamoto T. Angiogenesis induced by tissue factor in vitro and in vivo. Thromb Res 1999; 96: 183-9.