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Tissue Factor/VIIa in Thrombosis and Cancer

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Anticoagulants, Antiplatelets, and Thrombolytics

Part of the book series: Methods In Molecular Medicine™ ((MIMM,volume 93))

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Abstract

Tissue factor (TF) is a transmembrane glycoprotein that functions as a receptor and cofactor for activated factor VII (factor VIIa) to initiate blood coagulation. Although TF has been characterized best for its role in blood coagulation, recent studies have suggested a role for the molecule in physiologic processes that are distinct from hemostasis. Recently, this molecule has been shown to induce cellular signaling and promote angiogenesis and tumor metastasis (1–6).

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References

  1. Bromberg, M. E., Konigsberg, W. H., Madison, J. F., et al. (1995) Tissue factor promotes metastasis by a pathway independent of blood coagulation. Proc. Natl. Acad. Sci. USA 92, 8205–8209.

    Article  PubMed  CAS  Google Scholar 

  2. Bromberg, M. E., Sundaram, R., Homer, R. J., et al. (1999) Role of tissue factor in metastasis: function of the cytoplasmic and extracellular domains of the molecule. Thromb. Haemostasis 82, 88–92.

    CAS  Google Scholar 

  3. Bromberg, M. E., Bailly, M. A., and Konigsberg, W. H. (2001) Role of protease-activated receptor 1 in tumor metastasis promoted by tissue factor. Thromn. Haemostasis 86, 1210–1214.

    CAS  Google Scholar 

  4. Mousa, S. A. (2002) Anticoagulants in thrombosis and cancer: the missing link. Semin. Thromb. Hemost. 28(1), 45–52.

    Article  PubMed  CAS  Google Scholar 

  5. Mousa, S. A. and Mohamed, S. (2001) Anti-angiogenesis efficacy & mechanism of the low molecular weight heparin, tinzaparin and tissue factor pathway inhibitor (TFPI): potential anti-cancer benefits. Thromb. Haemostasis P1981.

    Google Scholar 

  6. Amirkhosravi, A., Francis, J., and Mousa, S. A. (2001) Anti-metastatic effect of low molecular weight heparin and tissue factor pathway inhibitor. Thromb. Haemostasis P1409.

    Google Scholar 

  7. Nemerson, Y. (1988) Tissue factor and hemostasis. Blood 71, 1–8.

    PubMed  CAS  Google Scholar 

  8. Paborsky, L. R., Caras, I. W., and Fisher, K. L. (1991) Lipid association, but not the transmembrane domain, is required for tissue factor activity. Substitution of the transmembrane domain with a phosphatidylinositol anchor. J. Biol. Chem. 266, 21,911–21,916.

    PubMed  CAS  Google Scholar 

  9. Zioncheck, T. F., Roy, S., and Behar, G. A. (1992) The cytoplasmic domain of tissue factor is phosphorylated by a protein kinase C-dependent mechanism. J. Biol. Chem. 267, 3561–3564.

    PubMed  CAS  Google Scholar 

  10. Mody, R. S. and Carson, S. D. (1997) Tissue factor cytoplasmic domain peptide is multiply phosphorylated in vitro. Biochemistry 36, 7869–7875.

    Article  PubMed  CAS  Google Scholar 

  11. Bazan, J. F (1990) Structural design and molecular evolution of a cytokine receptor superfamily. Proc. Natl. Acad. Sci. USA 87, 6934–6938.

    Article  PubMed  CAS  Google Scholar 

  12. Muller, Y. A., Ultsch, M. N., and deVos, A. M. (1996) The crystal structure of the extracellular domain of human tissue factor refined to 1.7 A resolution. J. Mol. Biol. 256, 144–159.

    Article  PubMed  CAS  Google Scholar 

  13. Broze, G. J. (1998) The tissue factor pathway of coagulation, in Thrombosis and Hemorrhage, Baltimore, MD, Williams and Wilkins, pp. 77–104.

    Google Scholar 

  14. Camerer, E., Rottingen, J. A., Iversen, J. G., et al. (1996) Coagulation factor VII and coagulation factor X induce Ca2+ oscillations in Madin-Darby canine kidney cells only when proteolytically active. J. Biol. Chem. 271, 29,034–29,042.

    Article  PubMed  CAS  Google Scholar 

  15. Masuda, M., Nakamura, S., Murakami, T, et al. (1996) Association of tissue factor with a gamma-chain homodimer of the IgE receptor-type I in cultured human monocytes. Eur. J. Immunol. 26, 2529–2532.

    Article  PubMed  CAS  Google Scholar 

  16. Poulsen, L. K., Jacobsen, N., Sorensen, N. C. H., et al. (1998) Signal transduction via the mitogen-activated protein kinase pathway induced by binding of coagulation factor VIIa to tissue factor. J. Biol. Chem. 273, 6228–6232.

    Article  PubMed  CAS  Google Scholar 

  17. Versteeg, H. H., Hoedemaeker, I., Diks, S. H., et al. (2000) FactorVIIa/tissue factor-induced signaling via activation of Src-like kinases, phosphatidylinositol 3-kinase, and Rac. J. Biol. Chem. 275, 28,750–28,756.

    Article  PubMed  CAS  Google Scholar 

  18. Pendurthi, U. R., Alok, D., and Rao, L. V M. (1997) Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase. Proc. Natl. Acad. Sci. USA 94, 12,598–12,603.

    Article  PubMed  CAS  Google Scholar 

  19. Ollivier, V., Bentolia, S., Chabbat, J., et al. (1998) Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII. Blood 91, 2698–2703.

    PubMed  CAS  Google Scholar 

  20. Taniguchi, T., Kakkar, A. K., Tuddenham, E. G. D., et al. (1998) Enhanced expression of urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. Cancer Res. 58, 4461–4467.

    PubMed  CAS  Google Scholar 

  21. Siegbahn, A., Johnell, M., Rorsman, C., et al. (2000) Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phopholipase C and enhanced PDGF-BB-stimulated chemotaxis. Blood 96, 3452–3458.

    PubMed  CAS  Google Scholar 

  22. Camerer, E., Rottingen, J.-A., Gjernes, E., Larsen, K., Skartlien, A. H., Iversen, J.-G., et al. (1999) Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene. J. Biol. Chem. 274, 32,225–32,233.

    Article  PubMed  CAS  Google Scholar 

  23. Pendurthi, U. R., Allen, K. E., Ezban, M., et al. (2000) 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-tissue factor-induced signal transduction. J. Biol. Chem. 14, 632–641.

    Google Scholar 

  24. Wojtukiewicz, M., Zacharski, L., Memoli, V., et al. (1990) Fibrinogen-fibrin transformation in situ in renal cell carcinoma. Anticancer Res. 10, 579–582.

    PubMed  CAS  Google Scholar 

  25. Zacharski, L., Wojtukiewicz, M., Costantini, V., et al. (1992) Pathways of coagulation/fibrinolysis activation in malignancy. Sem. Thromb. Hemost. 18, 104–116.

    Article  CAS  Google Scholar 

  26. Zacharski, L., Henderson, W., Rickles, F., et al. (1984) Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck and prostate. Cancer 53, 2046–2052.

    Article  PubMed  CAS  Google Scholar 

  27. Trousseau, A. (1865) Phlegmasia alba dolens. Clinique medicale de ľhotel-dieu de Paris. New Sydenham Society, London 3, 94.

    Google Scholar 

  28. Zacharski, L. and Meehan, K. (1993) Anticoagulants and cancer therapy. The Cancer Journal 6, 16–20.

    Google Scholar 

  29. Sorensen, H., Mellemkjaer, L., Olsen, J., and Baron, J. (2000) Prognosis of cancers associated with venous thromboembolism. N. Engl. J. Med. 343, 1846–1850.

    Article  PubMed  CAS  Google Scholar 

  30. Lebeau, B., Chastang, C., Brechot, J.-M., et al. (1994) Subcutaneous heparin treatment increases survival in small cell lung cancer. Cancer 74, 38–45.

    Article  PubMed  CAS  Google Scholar 

  31. Chahinian, A., Propert, K., Ware, J., et al. (1989) A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J. Clin. Oncol. 7, 993–1002.

    PubMed  CAS  Google Scholar 

  32. Thornes, R. (1983) Coumarins, melanoma and cellular immunity, in Protective Agents in Cancer (McBrien, D. and Slator, T., eds.), London, Academic Press, pp. 43–56.

    Google Scholar 

  33. Levine, M., Hirsh, J., Gent, M., et al. (1994) Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 343, 886–889.

    Article  PubMed  CAS  Google Scholar 

  34. Pinedo, H., Verheul, H., D’Amato, R., and Folkman, J. (1998) Involvement of platelets in tumour angiogenesis? Lancet 352, 1775–1777.

    Article  PubMed  CAS  Google Scholar 

  35. Ruf, W. and Edgington, T. S. (1991) An anti-tissue factor monoclonal antibody which inhibits TF-VIIa complex is a potent anticoagulant in plasma. Thromb. Haemostasis 66, 529–533.

    CAS  Google Scholar 

  36. Fiore, M. M., Neuenschwander, P. F., and Morrissey, J. H. (1992) An unusual antibody that blocks tissue factor/factor VIIa function by inhibiting cleavage only of macromolecular substrates. Blood 80, 3127–3134.

    PubMed  CAS  Google Scholar 

  37. Wun, T. C., Kretzmer, K. K., Palmier, M. O., et al. (1992) Comparison of recombinant tissue factor pathway inhibitors expressed in human SK hepatoma, mouse C127, baby hamster kidney, and Chinese hamster ovary cells. Thromb. Haemostasis 68, 54–59.

    CAS  Google Scholar 

  38. Kuenen, B. C., Levi, M., Meijers, J. C., Kakkar, A. K., van Hinsbergh, V. W., Kostense, P. J., et al. (2002) 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. Vase. Biol. 22(9), 1500–1505.

    Article  CAS  Google Scholar 

  39. Mousa, S. A., Bozarth, J., Larnkjaer, A., and Johanson, K. (2000) Vascular effects of heparin molecular weight fractions and LMWH on the release of TFPI from human endothelial cells. Blood 16(11), 59, 3928.

    Google Scholar 

  40. Marutsuka, K., Hatakeyama, K., Sato, Y., Yamashita, A., Sumiyoshi, A., and Asada, Y (2002) Protease-activated receptor 2 (PAR2) mediates vascular smooth muscle cell migration induced by tissue factor/factor Vila complex. Thromb. Res. 107(5), 271–276.

    Article  PubMed  CAS  Google Scholar 

  41. Siegbahn, A., Johnell, M., Rorsman, C., Ezban, M., Heldin, C. H., and Ronnstrand, L. (2000) Binding of factor Vila to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemotaxis. Blood 96(10), 3452–3458.

    PubMed  CAS  Google Scholar 

  42. Abe, K., Shoji, M., Chen, J., Bierhaus, A., Danave, I., Micko, C., et al. (1999) Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc. Natl. Acad. Sci. USA 96(15), 8663–8668.

    Article  PubMed  CAS  Google Scholar 

  43. Takano, S., Tsuboi, K., Tomono, Y., Mitsui, Y., and Nose, T. (2000) Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br. J. Cancer 82(12), 1967–1973.

    Article  PubMed  CAS  Google Scholar 

  44. Seto, S., Onodera, H., Kaido, T., Yoshikawa, A., Ishigami, S., Arii, S., et al. (2000) Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis. Cancer 88(2), 295–301.

    Article  PubMed  CAS  Google Scholar 

  45. Dupont, E., Falardeau, P., Mousa, S. A., Dimitriadou, V., Pepin, M. C, Wang, T., et al. (2002) Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue. Clin. Exp. Metastasis 19(2), 145–153.

    Article  PubMed  CAS  Google Scholar 

  46. Kim, S., Mousa, S. A., and Varner, J. (2000) Requirement of integrin α5β1 and its ligand fibronectin in angiogenesis. Am. J. Pathol. 156, 1345–1362.

    Article  PubMed  CAS  Google Scholar 

  47. Colman, R. W., Pixley, R. A., Sainz, I. M., Song, J. S., Isordia-Salas, Mohamed, S., et al. (2003) Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen. J. Thromb. Haemostasis 1(1), 164–173.

    Article  CAS  Google Scholar 

  48. Van Waes, C., Enamorado, D., Hecht, I., Sulica, L., Chen, Z., Batt, D., et al. (2000) Effects of the novel αv integrin antagonist SM256 and cis-platinum on growth of murine squamous cell carcinoma PAMLY8. Int. J. Oncol. 16(6), 1189–1195.

    PubMed  Google Scholar 

  49. Ali, S., O’Dounell, A., Balu, D., Pohl, M., Seyler, M., Mohamed, S., et al. (2000) Estrogen receptor-α in the inhibition of cancer growth and angiogenesis. Cancer Res. 60, 7094–7098.

    PubMed  CAS  Google Scholar 

  50. Luna, J., Tobe, T., Mousa, S. A., Reilly, T., and Campochiaro, P. (1996) Antagonist of Integrin αvβ3 Inhibit Retinal Neovascularization in Murine Model. Lab. Investig. 75(4), 563–573.

    PubMed  CAS  Google Scholar 

  51. Chen, Z., Malhotra, P., Thomas, G., Ondrey, F., Duffey, D., Smith, C., et al. (1999) Expression of pro-inflammatory and pro-angiogenic cytokines in patients with head and neck cancer. Clinical Cancer Res. (5), 1369–1379.

    CAS  Google Scholar 

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  1. Albany College of Pharmacy, Albany, NY

    Shaker A. Mousa

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  1. Albany College of Pharmacy, Albany, NY

    Shaker A. Mousa

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Mousa, S.A. (2004). Tissue Factor/VIIa in Thrombosis and Cancer. In: Mousa, S.A. (eds) Anticoagulants, Antiplatelets, and Thrombolytics. Methods In Molecular Medicine™, vol 93. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-658-4:119

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  • DOI: https://doi.org/10.1385/1-59259-658-4:119

  • Publisher Name: Springer, Totowa, NJ

  • Print ISBN: 978-1-58829-083-0

  • Online ISBN: 978-1-59259-658-4

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