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Semin Thromb Hemost 2004; 30(1): 21-30
DOI: 10.1055/s-2004-822968
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Oncogenes as Regulators of Tissue Factor Expression in Cancer: Implications for Tumor Angiogenesis and Anti-Cancer Therapy

Joanne L. Yu1 , Linda May1 , Petr Klement1 , Jeffrey I. Weitz1 , Janusz Rak1 , 2
  • 1Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, Ontario, Canada
  • 2Assistant Professor of Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, Ontario, Canada
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Publikationsverlauf

Publikationsdatum:
22. März 2004 (online)

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Up-regulation of tissue factor (TF) is often observed in cancer. TF is a cell-associated receptor for coagulation factor VII/VIIa, an interaction known to activate the coagulation cascade. At the same time, TF is also known as a mediator of intracellular signaling events that can alter gene expression patterns and cell behavior. Both aspects of TF activity are of possible relevance to tumor growth, metastasis, and angiogenesis, including up-regulation of vascular endothelial growth factor (VEGF). TF up-regulation is often observed on the surfaces of tumor-associated endothelial cells, inflammatory cells, and particularly on cancer cells themselves. In the last case, high TF levels may be associated with poor prognosis and parallel clinical (and genetic) tumor progression. We have proposed elsewhere that TF may be a target of oncogenic events in cancer. Here we discuss our observations suggesting that oncogene-targeting agents may down-regulate TF expression. Such is the effect of treatment with the neutralizing monoclonal antibody (C225) raised against the epidermal growth factor receptor (EGFR) in EGFR-dependent squamous cell carcinoma cells (A431). This two- to threefold TF down-regulation by C225 treatment is paralleled by a decrease in expression of VEGF. It is conceivable that TF participates in signals that regulate VEGF and angiogenesis triggered by activated oncogenic pathways. Therefore, direct targeting of TF in cancer should be considered in combination with other treatment modalities such as oncogene-directed therapies, antiangiogenic agents (e.g., VEGF antagonists), and anti-cancer chemotherapy.

KEYWORDS

Tissue factor - cancer - angiogenesis - oncogenes - EGFR

REFERENCES

  • 1 Fearon E R, Vogelstein B. A genetic model for colorectal tumorigenesis.  Cell. 1990;  61 759-767
    CrossrefPubMedGoogle Scholar
  • 2 Done S, Squire J A. Genetic basis of cancer progression. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 3-18
    Google Scholar
  • 3 McCormick F. Signal transduction networks. Ras as a paradigm. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 35-46
    Google Scholar
  • 4 Holland E C. The interplay between tumor suppressor genes and oncogenes in tumorigenesis. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 101-112
    Google Scholar
  • 5 Hahn W C, Counter C M, Lundberg A S, Beijersbergen R L, Brooks M W, Weinberg R A. Creation of human tumour cells with defined genetic elements.  Nature. 1999;  400 464-468
    CrossrefPubMedGoogle Scholar
  • 6 Hanahan D, Weinberg R A. The hallmarks of cancer.  Cell. 2000;  100 57-70
    CrossrefPubMedGoogle Scholar
  • 7 Folkman J. Tumor angiogenesis. In: Holland JF, Bast RC, Morton DL, Frei E, Kufe DW, Weichselbaum RR Cancer Medicine. Baltimore; Williams & Wilkins 1997: 181-204
    Google Scholar
  • 8 Trousseau A. Phlegmasia alba dolens. In: Clinique Medicale de l'Hôtel-Dieu de Paris. London; The New Sydenham Society 1865: 94-96
    Google Scholar
  • 9 Browder T, Folkman J, Pirie-Shepherd S. The hemostatic system as a regulator of angiogenesis.  J Biol Chem. 2000;  275 1521-1524
    CrossrefPubMedGoogle Scholar
  • 10 Wojtukiewicz M Z, Sierko E, Klement P, Rak J. The hemostatic system and angiogenesis in malignancy.  Neoplasia. 2001;  3 371-384
    Google Scholar
  • 11 Folkman J. What is the evidence that tumors are angiogenesis-dependent?.  J Natl Cancer Inst. 1990;  82 4-6
    CrossrefPubMedGoogle Scholar
  • 12 Alitalo K, Carmeliet P. Molecular mechanisms of lymphangiogenesis in health and disease.  Cancer Cell. 2002;  1 219-227
    CrossrefPubMedGoogle Scholar
  • 13 Rak J, Filmus J, Kerbel R S. Reciprocal paracrine interactions between tumor cells and endothelial cells. The “angiogenesis progression” hypothesis.  Eur J Cancer. 1996;  32A 2438-2450
    PubMedGoogle Scholar
  • 14 Hamada J, Cavanaugh P G, Miki K, Nicolson G L. A paracrine migration-stimulating factor for metastatic tumor cells secreted by mouse hepatic sinusoidal endothelial cells: identification as complement component C3b.  Cancer Res. 1993;  53 4418-4423
    PubMedGoogle Scholar
  • 15 Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig N E. Halting angiogenesis suppresses carcinoma cell invasion.  Nat Med. 1997;  3 1222-1227
    CrossrefPubMedGoogle Scholar
  • 16 Brooks P C, Stromblad S, Klemke R, Visscher D, Sarkar F H, Cheresh D A. Antiintegrin αbβ3 blocks human breast cancer growth and angiogenesis in human skin.  J Clin Invest. 1995;  96 1815-1822
    CrossrefPubMedGoogle Scholar
  • 17 Nicosia R F, Tchao R, Leighton J. Angiogenesis-dependent tumor spread in reinforced fibrin clot culture.  Cancer Res. 1983;  43 2159-2166
    PubMedGoogle Scholar
  • 18 Rak J W, Hegmann E J, Lu C, Kerbel R S. Progressive loss of sensitivity to endothelium-derived growth inhibitors expressed by human melanoma cells during disease progression.  J Cell Physiol. 1994;  159 245-255
    CrossrefPubMedGoogle Scholar
  • 19 Folkman J. Tumor angiogenesis.  Adv Cancer Res. 1985;  43 175-203
    PubMedGoogle Scholar
  • 20 Holash J, Maisonpierre P C, Compton D et al.. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF.  Science. 1999;  284 1994-1998
    CrossrefPubMedGoogle Scholar
  • 21 Rak J, Kerbel R S. Oncogenes and tumor angiogenesis. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 171-218
    Google Scholar
  • 22 Bouck N, Stellmach V, Hsu S C. How tumors become angiogenic.  Adv Cancer Res. 1996;  69 135-174
    PubMedGoogle Scholar
  • 23 Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.  Cell. 1996;  86 353-364
    CrossrefPubMedGoogle Scholar
  • 24 Nash G F, Walsh D C, Kakkar A K. The role of the coagulation system in tumour angiogenesis.  Lancet Oncol. 2001;  2 608-613
    CrossrefPubMedGoogle Scholar
  • 25 O'Reilly M S, Pirie-Shepherd S, Lane W S, Folkman J. Antiangiogenic activity of the cleaved conformation of the serpin antithrombin.  Science. 1999;  285 1926-1928
    CrossrefPubMedGoogle Scholar
  • 26 Cao Y. Endogenous angiogenesis inhibitors and their therapeutic implications.  Int J Biochem Cell Biol. 2001;  33 357-369
    CrossrefPubMedGoogle Scholar
  • 27 Gimbrone M, Leapman S, Cotran R, Folkman J. Tumor dormancy in vivo by prevention of neovascularization.  J Exp Med. 1972;  136 261-276
    CrossrefPubMedGoogle Scholar
  • 28 Holmgren L, O'Reilly M S, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression.  Nat Med. 1995;  1 149-153
    PubMedGoogle Scholar
  • 29 Hanahan D. Signaling vascular morphogenesis and maintenance.  Science. 1997;  277 48-50
    CrossrefPubMedGoogle Scholar
  • 30 Rak J, Kerbel R S. Prospects and progress in the development of anti-angiogenic agents. In: Rosenberg SA Principles and Practice of Biologic Therapy of Cancer-Updates 3[3]. New York; Lippincott, Williams & Wilkins 2002: 1-13
    Google Scholar
  • 31 Yancopoulos G D, Davis S, Gale N W, Rudge J S, Wiegand S J, Holash J. Vascular-specific growth factors and blood vessel formation.  Nature. 2000;  407 242-248
    CrossrefPubMedGoogle Scholar
  • 32 Carmeliet P. Mechanisms of angiogenesis and arteriogenesis.  Nat Med. 2000;  6 389-395
    CrossrefPubMedGoogle Scholar
  • 33 Carmeliet P, Jain R K. Angiogenesis in cancer and other diseases.  Nature. 2000;  407 249-257
    CrossrefPubMedGoogle Scholar
  • 34 Folkman J, D'Amore P A. Blood vessel formation: what is its molecular basis?.  Cell. 1996;  87 1153-1155
    CrossrefPubMedGoogle Scholar
  • 35 LeCouter J, Kowalski J, Foster J et al.. Identification of an angiogenic mitogen selective for endocrine gland endothelium.  Nature. 2001;  412 877-884
    CrossrefPubMedGoogle Scholar
  • 36 Ferrara N, Gerber H P. The role of vascular endothelial growth factor in angiogenesis.  Acta Haematol. 2001;  106 148-156
    CrossrefPubMedGoogle Scholar
  • 37 LeCouter J, Lin R, Ferrara N. Endocrine gland-derived VEGF and the emerging hypothesis of organ-specific regulation of angiogenesis.  Nat Med. 2002;  8 913-917
    PubMedGoogle Scholar
  • 38 Jones N, Iljin K, Dumont D J, Alitalo K. Tie receptors: new modulators of angiogenic and lymphangiogenic responses.  Nat Rev Mol Cell Biol. 2001;  2 257-267
    CrossrefPubMedGoogle Scholar
  • 39 Wang H U, Chen Z F, Anderson D J. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4.  Cell. 1998;  93 741-753
    CrossrefPubMedGoogle Scholar
  • 40 Dvorak H F, Brown L F, Detmar M, Dvorak A M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis [review].  Am J Pathol. 1995;  146 1029-1039
    PubMedGoogle Scholar
  • 41 Ferrara N. VEGF and the quest for tumour angiogenesis factors.  Nat Rev Cancer. 2002;  2 795-803
    CrossrefPubMedGoogle Scholar
  • 42 Senger D R, Galli S, Dvorak A M, Perruzzi C A, Harvey V S, Dvorak H F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.  Science. 1983;  219 983-985
    CrossrefPubMedGoogle Scholar
  • 43 Leung D W, Cachianes G, Kuang W J, Goeddel D V, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen.  Science. 1989;  246 1306-1309
    CrossrefPubMedGoogle Scholar
  • 44 Ferrara N, Carver-Moore K, Chen H et al.. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.  Nature. 1996;  380 439-442
    CrossrefPubMedGoogle Scholar
  • 45 Carmeliet P, Ferreira V, Breier G et al.. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele.  Nature. 1996;  380 435-439
    CrossrefPubMedGoogle Scholar
  • 46 Fong G H, Rossant J, Gertsenstein M, Breitman M L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium.  Nature. 1995;  376 66-70
    CrossrefPubMedGoogle Scholar
  • 47 Shalaby F, Rossant J, Yamaguchi T P et al.. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice.  Nature. 1995;  376 62-66
    CrossrefPubMedGoogle Scholar
  • 48 Alon T, Hemo I, Itin A, Pe'er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity.  Nat Med. 1995;  1 1024-1028
    CrossrefPubMedGoogle Scholar
  • 49 Watanabe Y, Lee S W, Detmar M, Ajioka I, Dvorak H F. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells.  Oncogene. 1997;  14 2025-2032
    CrossrefPubMedGoogle Scholar
  • 50 Asahara T, Takahashi T, Masuda H et al.. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells.  EMBO J. 1999;  18 3964-3972
    CrossrefPubMedGoogle Scholar
  • 51 Hattori K, Dias S, Heissig B et al.. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells.  J Exp Med. 2001;  193 1005-1014
    CrossrefPubMedGoogle Scholar
  • 52 Pettersson A, Nagy J A, Brown L F et al.. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor.  Lab Invest. 2000;  80 99-115
    CrossrefPubMedGoogle Scholar
  • 53 Jain R K. Transport of molecules in the tumor interstitium: a review.  Cancer Res. 1987;  47 3039-3051
    PubMedGoogle Scholar
  • 54 Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications.  Semin Oncol. 2002;  29 10-14
    PubMedGoogle Scholar
  • 55 Ollivier V, Chabbat J, Herbert J M, 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 1374-1381
    PubMedGoogle Scholar
  • 56 Bergers G, Brekken R, McMahon G et al.. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis.  Nat Cell Biol. 2000;  2 737-744
    CrossrefPubMedGoogle Scholar
  • 57 Rak J, Mitsuhashi Y, Bayko L, Filmus J, Sasazuki T, Kerbel R S. Mutant ras oncogenes up-regulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis.  Cancer Res. 1995;  55 4575-4580
    PubMedGoogle Scholar
  • 58 Viloria-Petit A M, Rak J, Hung M-C, Rockwell P, Goldstein N, Kerbel R S. Neutralizing antibodies against EGF and ErbB-2/neu receptor tyrosine kinases down-regulate VEGF production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors.  Am J Pathol. 1997;  151 1523-1530
    PubMedGoogle Scholar
  • 59 Feldkamp M M, Lau N, Rak J, Kerbel R S, Guha A. Normoxic and hypoxic regulation of vascular endothelial growth factor (VEGF) by astrocytoma cells is mediated by Ras.  Int J Cancer. 1999;  81 118-124
    CrossrefPubMedGoogle Scholar
  • 60 Rak J, Mitsuhashi Y, Sheehan C et al.. Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts.  Cancer Res. 2000;  60 490-498
    PubMedGoogle Scholar
  • 61 Viloria-Petit A, Crombet T, Jothy S et al.. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis.  Cancer Res. 2001;  61 5090-5101
    PubMedGoogle Scholar
  • 62 Rak J, Yu J L, Klement G, Kerbel R S. Oncogenes and angiogenesis: signaling three-dimensional tumor growth.  J Investig Dermatol Symp Proc. 2000;  5 24-33
    CrossrefPubMedGoogle Scholar
  • 63 Mazure N M, Chen E Y, Laderoute K R, Giaccia A J. Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element.  Blood. 1997;  90 3322-3331
    PubMedGoogle Scholar
  • 64 Sodhi A, Montaner S, Miyazaki H, Gutkind J S. MAPK and Akt act cooperatively but independently on hypoxia inducible factor-1 alpha in rasV12 up-regulation of VEGF.  Biochem Biophys Res Commun. 2001;  287 292-300
    CrossrefPubMedGoogle Scholar
  • 65 Maity A, Pore N, Lee J, Solomon D, O'Rourke D M. Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia.  Cancer Res. 2000;  60 5879-5886
    PubMedGoogle Scholar
  • 66 Semenza G L. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression.  Crit Rev Biochem Mol Biol. 2000;  35 71-103
    CrossrefPubMedGoogle Scholar
  • 67 Dvorak H F, Dvorak A M, Manseau E J, Wiberg L, Churchill W H. Fibrin gel investment associated with line 1 and line 10 solid tumor growth, angiogenesis, and fibroplasia in guinea pigs. Role of cellular immunity, myofibroblasts, microvascular damage, and infarction in line 1 tumor regression.  J Natl Cancer Inst. 1979;  62 1459-1472
    PubMedGoogle Scholar
  • 68 Palumbo J S, Kombrinck K W, Drew A F et al.. Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells.  Blood. 2000;  96 3302-3309
    Google Scholar
  • 69 Dvorak F H. Abnormalities of hemostasis in malignant disease. In: Coleman RB, Hirsh J, Marder VJ, Salzman JB Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia; Lippincott Co 1994: 1238-1254
    Google Scholar
  • 70 Rickles F R, Shoji M, Abe K. The role of the hemostatic system in tumor growth, metastasis, and angiogenesis: tissue factor is a bifunctional molecule capable of inducing both fibrin deposition and angiogenesis in cancer.  Int J Hematol. 2001;  73 145-150
    CrossrefPubMedGoogle Scholar
  • 71 Mackman N. Gene targeting in hemostasis. Tissue factor.  Front Biosci. 2001;  6 D208-D215
    PubMedGoogle Scholar
  • 72 Fernandez P M, Rickles F R. Tissue factor and angiogenesis in cancer.  Curr Opin Hematol. 2002;  9 401-406
    CrossrefPubMedGoogle Scholar
  • 73 Morrissey J H. Tissue factor: an enzyme cofactor and a true receptor.  Thromb Haemost. 2001;  86 66-74
    PubMedGoogle Scholar
  • 74 Kaplan R, DeLa Cadena R A. Mechanism of the coagulopathy associated with acute promyelocytic leukemia-clinical conference.  Am J Hematol. 1998;  59 234-237
    CrossrefPubMedGoogle Scholar
  • 75 Lee A Y. Cancer and thromboembolic disease: pathogenic mechanisms.  Cancer Treat Rev. 2002;  28 137-140
    CrossrefPubMedGoogle Scholar
  • 76 Rickles F R, Levine M N. Epidemiology of thrombosis in cancer.  Acta Haematol. 2001;  106 6-12
    Google Scholar
  • 77 Levine M. Thromboembolic risk of tamoxifen in patients with stage II breast cancer.  J Clin Oncol. 1989;  7 1579-1580
    PubMedGoogle Scholar
  • 78 Levine M N, Gent M, Hirsh J et al.. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer.  N Engl J Med. 1988;  318 404-407
    CrossrefPubMedGoogle Scholar
  • 79 Kuenen B C, Levi M, Meijers J C et al.. Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients.  Arterioscler Thromb Vasc Biol. 2002;  22 1500-1505
    PubMedGoogle Scholar
  • 80 Kuenen B C, Rosen L, Smit E F et al.. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors.  J Clin Oncol. 2002;  20 1657-1667
    CrossrefPubMedGoogle Scholar
  • 81 Zacharski L R, Costantini V, Wojtukiewicz M Z, Memoli V A, Kudryk B J. Anticoagulants as cancer therapy.  Semin Oncol. 1990;  17 217-227
    PubMedGoogle Scholar
  • 82 Thodiyil P, Kakkar A K. Can low-molecular-weight heparins improve outcome in patients with cancer?.  Cancer Treat Rev. 2002;  28 151-155
    CrossrefPubMedGoogle Scholar
  • 83 Contrino J, Hair G, Kreutzer D L, Rickles F R. In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease.  Nat Med. 1996;  2 209-215
    CrossrefPubMedGoogle Scholar
  • 84 Shoji M, Hancock W W, Abe K 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
    PubMedGoogle Scholar
  • 85 Abe K, Shoji M, Chen J 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 8663-8668
    Google Scholar
  • 86 Ruf W, Mueller B M. Tissue factor in cancer angiogenesis and metastasis.  Curr Opin Hematol. 1996;  3 379-384
    CrossrefPubMedGoogle Scholar
  • 87 Zhang Y, Deng Y, Luther T et al.. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice.  J Clin Invest. 1994;  94 1320-1327
    Google Scholar
  • 88 Chen J, Bierhaus A, Schiekofer S et al.. Tissue factor-a receptor involved in the control of cellular properties, including angiogenesis.  Thromb Haemost. 2001;  86 334-345
    PubMedGoogle Scholar
  • 89 Mackman N, Morrissey J H, Fowler B, Edgington T S. Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade.  Biochemistry. 1989;  28 1755-1762
    CrossrefPubMedGoogle Scholar
  • 90 Giesen P L, Rauch U, Bohrmann B et al.. Blood-borne tissue factor: another view of thrombosis.  Proc Natl Acad Sci USA. 1999;  96 2311-2315
    Google Scholar
  • 91 Colman R W, Marder V J, Salzman E W, Hirsh J. Overview of Hemostasis. In: Coleman RB, Hirsh J, Marder VJ, Salzman JB Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia; Lippincott Co 1994: 3-18
    Google Scholar
  • 92 Rak J, Klement G. Impact of oncogenes and tumor suppressor genes on deregulation of hemostasis and angiogenesis in cancer.  Cancer Metastasis Rev. 2000;  19 93-96
    CrossrefPubMedGoogle Scholar
  • 93 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;  83 164-170
    Google Scholar
  • 94 Sawada M, Miyake S, Ohdama S et al.. Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis.  Br J Cancer. 1999;  79 472-477
    Google Scholar
  • 95 Kakkar A K, Lemoine N R, Scully M F, Tebbutt S, Williamson R C. Tissue factor expression correlates with histological grade in human pancreatic cancer.  Br J Surg. 1995;  82 1101-1104
    CrossrefPubMedGoogle Scholar
  • 96 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
    CrossrefPubMedGoogle Scholar
  • 97 Seto S, Onodera H, Kaido T et al.. Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis.  Cancer. 2000;  88 295-301
    CrossrefPubMedGoogle Scholar
  • 98 Shigemori C, Wada H, Matsumoto K, Shiku H, Nakamura S, Suzuki H. Tissue factor expression and metastatic potential of colorectal cancer.  Thromb Haemost. 1998;  80 894-898
    PubMedGoogle Scholar
  • 99 Nakasaki T, Wada H, Shigemori C et al.. Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer.  Am J Hematol. 2002;  69 247-254
    Google Scholar
  • 100 Mueller B M, Reisfeld R A, Edgington T S, Ruf W. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis.  Proc Natl Acad Sci USA. 1992;  89 11832-11836
    PubMedGoogle Scholar
  • 101 Francis J L, Amirkhosravi A. Effect of antihemostatic agents on experimental tumor dissemination.  Semin Thromb Hemost. 2002;  28 29-38
    Google Scholar
  • 102 Bromberg M E, Sundaram R, Homer R J, Garen A, Konigsberg W H. Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule.  Thromb Haemost. 1999;  82 88-92
    PubMedGoogle Scholar
  • 103 Rottingen 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 4650-4660
    CrossrefPubMedGoogle Scholar
  • 104 Rottingen J A, Camerer E, Mathiesen I, Prydz H, Iversen J G. Synchronized Ca2+ oscillations induced in Madin Darby canine kidney cells by bradykinin and thrombin but not by ATP.  Cell Calcium. 1997;  21 195-211
    CrossrefPubMedGoogle Scholar
  • 105 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 6580-6585
    CrossrefPubMedGoogle Scholar
  • 106 Prydz H, Camerer E, Rottingen J A, Wiiger M T, Gjernes E. Cellular consequences of the initiation of blood coagulation.  Thromb Haemost. 1999;  82 183-192
    PubMedGoogle Scholar
  • 107 Camerer E, Rottingen 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 29034-29042
    CrossrefPubMedGoogle Scholar
  • 108 Camerer E, Rottingen J A, Gjernes E et al.. Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene.  J Biol Chem. 1999;  274 32225-32233
    CrossrefPubMedGoogle Scholar
  • 109 Herbert J M, de Prost D, Ollivier V, Melis E, Carmeliet P. Tissue factor is not involved in the mitogenic activity of factor VIIa.  Biochem Biophys Res Commun. 2001;  281 1074-1077
    CrossrefPubMedGoogle Scholar
  • 110 Contrino J, Goralnick S, Qi J, Hair G, Rickles F R, Kreutzer D L. Fibrin induction of tissue factor expression in human vascular endothelial cells.  Circulation. 1997;  96 605-613
    PubMedGoogle Scholar
  • 111 Jahner D, Hunter T. The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein-tyrosine kinases leads to the induction of a subset of immediate early genes.  Oncogene. 1991;  6 1259-1268
    PubMedGoogle Scholar
  • 112 Mackman N. Regulation of the tissue factor gene.  Thromb Haemost. 1997;  78 747-754
    PubMedGoogle Scholar
  • 113 Carson S D, Bromberg M E. Tissue factor encryption/de-encryption is not altered in the absence of the cytoplasmic domain.  Thromb Haemost. 2000;  84 657-663
    PubMedGoogle Scholar
  • 114 Wolberg A S, Kon R H, Monroe D M, Ezban M, Roberts H R, Hoffman M. De-encryption of cellular tissue factor is independent of its cytoplasmic domain.  Biochem Biophys Res Commun. 2000;  272 332-336
    CrossrefPubMedGoogle Scholar
  • 115 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 2698-2703
    PubMedGoogle Scholar
  • 116 Pandolfi P P. Oncogenes and tumor suppressors in the molecular pathogenesis of acute promyelocytic leukemia.  Hum Mol Genet. 2001;  10 769-775
    CrossrefPubMedGoogle Scholar
  • 117 Koyama T, Hirosawa S, Kawamata N, Tohda S, Aoki N. All-trans retinoic acid up-regulates thrombomodulin and down-regulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells.  Blood. 1994;  84 3001-3009
    PubMedGoogle Scholar
  • 118 Lopez-Pedrera C, Dobado-Berrios P M, Ros R et al.. Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP.  Thromb Haemost. 2001;  85 1031-1036
    PubMedGoogle Scholar
  • 119 Kini A R, Peterson L C, Tallman M S, Lingen M W. Angiogenesis in acute promyelocytic leukemia: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid.  Blood. 2001;  97 3919-3924
    CrossrefPubMedGoogle Scholar
  • 120 Fletcher L. Approval heralds new generation of kinase inhibitors?.  Nat Biotechnol. 2001;  19 599-600
    PubMedGoogle Scholar
  • 121 Konecny G E, Arboleda J, Slamon D, Pegram M. Inhibition of the HER-2 oncogene: A translational research model for the development of future targeted therapies. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 331-352
    Google Scholar
  • 122 Lin E H, Abbruzzese J. Clinical evaluation of agents targeting epidermal growth factor receptor (EGFR) in cancer. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 313-330
    Google Scholar
  • 123 Cox A D. Farnesyltransferase inhibitors as anticancer agents. In: Rak J Oncogene-Directed Therapies. Totowa, NJ; Humana Press 2003: 353-362
    Google Scholar
  • 124 Bykov V J, Issaeva N, Shilov A et al.. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound.  Nat Med. 2002;  8 282-288
    PubMedGoogle Scholar
  • 125 Izumi H, Takahashi C, Oh J, Noda M. Tissue factor pathway inhibitor-2 suppresses the production of active matrix metalloproteinase-2 and is down-regulated in cells harboring activated ras oncogenes.  FEBS Lett. 2000;  481 31-36
    CrossrefPubMedGoogle Scholar
  • 126 Lengyel E, Ried S, Heiss M M, Jager C, Schmitt M, Allgayer H. Ras regulation of urokinase-type plasminogen activator.  Methods Enzymol. 2001;  333 105-116
    PubMedGoogle Scholar

Janusz RakM.D. Ph.D. 

Henderson Research Centre

Room 216, 711 Concession Street

Hamilton, Ontario, L8V 1C3, Canada

eMail: jrak@thrombosis.hhscr.org

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