Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Leukemia volume 20, pages 1331–1340 (2006)Cite this article

Abstract

In the last few years, it has become clear that the processes of tumor angiogenesis, metastasis and invasiveness are highly dependent on components of the blood coagulation cascade. One of the key proteins in coagulation is tissue factor (TF). In addition, TF is also known as a mediator of intracellular signaling events that can alter gene expression patterns and cell behavior. TF significantly participates in tumor-associated angiogenesis and its expression levels have been correlated with the metastatic potential of many types of hematological malignancies. Signaling pathways initiated by both, tissue factor-activated factor VII (TF-FVII(a)) protease activation of protein-activated receptors (PARs), and phosphorylation of the TF-cytoplasmic domain, appear to regulate these tumoral functions. Advances in antiangiogenic therapies and preclinical studies with TF-targeted therapeutics are hopeful in the control of tumor growth and metastasis, but continued studies on the regulation of TF are still needed. In the last few years, the use of approaches of functional genomics and proteomics has allowed the discovery of new proteins involved in the origin of the neoplasia and their participation in the development of the disease. This review attempts to establish a cellular and molecular causal link between cancer coagulopathy, angiogenesis and tumor progression in hematological malignancies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Versteeg HH, Peppelenbosch MP, Spek CA . The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling? Thromb Haemost 2001; 86: 1353–1359.

    Article  CAS  PubMed  Google Scholar 

  2. Ruf W, Edgington TS . Structural biology of TF, the initiator of thrombogenesis in vivo. FASEB J 1994; 8: 385–390.

    Article  CAS  PubMed  Google Scholar 

  3. Peppelenbosch MP, Versteeg HH . Cell biology of tissue factor, and unusual member of the cytokine receptor family. Trends Cardiovasc Med 2001; 11: 335–339.

    Article  CAS  PubMed  Google Scholar 

  4. Drake TA, Morrisey JH, Edgington TS . Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134: 1087–1097.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen J, Bierhaus A, Schiekofer S, Andrassy M, Chen B, Stern DM et al. Tissue factor – a receptor involved in the control of cellular properties, including angiogenesis. Thromb Haemost 2001; 86: 334–345.

    Article  CAS  PubMed  Google Scholar 

  6. Versteeg HH, Spek CA, Peppelenbosch MP, Richel DJ . Tissue factor and cancer metastasis: the role of intracellular and extracellular signalling pathways. Mol Med 2004; 10: 6–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sampson MT, Kakkar AK . Coagulation proteases and human cancer. Biochem Soc Trans 2002; 30: 201–207.

    Article  CAS  PubMed  Google Scholar 

  8. Rickles FR, Shoji M, Abe K . The role of the hemostatic system in tumor growth, metastasis, and angiogenesis: TF is a bifunctional molecule capable of inducing both fibrin deposition and angiogenesis in cancer. Int J Hematol 2001; 73: 145–150.

    Article  CAS  PubMed  Google Scholar 

  9. Coughlin SR . Thrombin signalling and protease-activated-receptors. Nature 2000; 407: 258–264.

    Article  CAS  PubMed  Google Scholar 

  10. Cupit LD, Schmidt VA, Gnatenko DV, Bahou WF . Expression of protease activated receptor 3 (PAR3) is upregulated by induction of megakaryocyte phenotype in human erythroleukemia (HEL) cells. Exp Hematol 2004; 32: 991–999.

    Article  CAS  PubMed  Google Scholar 

  11. Schiller H, Bartscht T, Arlt A, Zahn MO, Seifert A, Bruhn T et al. Thrombin as a survival factor for cancer cells: thrombin activation in malignant effusions in vivo and inhibition of idarubidin-induced cell death in vitro. Int J Clin Pharmacol Ther 2002; 40: 329–335.

    Article  CAS  PubMed  Google Scholar 

  12. Naldini A, Sower L, Bocci V, Meyers B, Carney DH . Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation. J Cell Physiol 1998; 177: 76–84.

    Article  CAS  PubMed  Google Scholar 

  13. Shi X, Gangadharan B, Brass LF, Ruf W, Mueller BM . Protease-activated receptors (PAR1 and PAR2) contribute to tumor cell motility and metastasis. Mol Cancer Res 2004; 2: 395–402.

    CAS  PubMed  Google Scholar 

  14. Yin Y-J, Salah Z, Maoz M, Cohen Even Ram S, Ochayon S, Neufeld G et al. Oncogenic transformation induces tumor angiogenesis: a role for PAR1 activation. FASEB J 2003; 17: 163–174.

    Article  CAS  PubMed  Google Scholar 

  15. Tallman MS, Kwaan HC . Intravascular clotting activation and bleeding in patients with hematologic malignancies. Rev Clin Exp Hematol 2004; 8: E1.

    PubMed  Google Scholar 

  16. Sase T, Wada H, Yamaguchi M, Ogawa S, Kamidura Y, Nishikawa M et al. Haemostatic abnormalities and thrombotic disorders in malignant lymphoma. Thomb Haemost 2005; 93: 153–159.

    Article  CAS  Google Scholar 

  17. Semeraro N, Montemurro P, Giordano P, Santoro N, De Mattia D, Colucci M . Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma. Thromb Haemost 1994; 72: 54–57.

    CAS  PubMed  Google Scholar 

  18. Wada H, Sase T, Yamaguchi M . Hypercoagulant states in malignant lymphoma. Exp Oncol 2005; 27: 179–185.

    CAS  PubMed  Google Scholar 

  19. López-Pedrera CH, Jardí M, Malagón MM, Inglés-Esteve J, Dorado G, Torres A et al. Involvement of tissue factor (TF) and urokinase receptor (uPAR) in bleeding complications of leukemic patients. Thromb Haemost 1997; 771: 62–70.

    Google Scholar 

  20. Nadir Y, Katz T, Sarig G, Hoffman R, Oliven A, Rowe JM et al. Hemostatic balance on the surface of leukemic cells: the role of tissue factor and urokinase plasminogen activator receptor. Haematologica 2005; 90: 1549–1556.

    CAS  PubMed  Google Scholar 

  21. Zangari M, Saghafifar F, Mehta P, Barlogie B, Fink L, Tricot G . The blood coagulation mechanism in multiple myeloma. Semin Thromb Hemost 2003; 29: 275–282.

    Article  CAS  PubMed  Google Scholar 

  22. Yu JL, May L, Lhotak V, Shahrzad S, Shirasawa S, Weitz JI et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 2005; 105: 1734–1741.

    Article  CAS  PubMed  Google Scholar 

  23. Browder T, Folkman J, Pirie-Shepherd S . The hemostatic system as a regulator of angiogenesis. J Biol Chem 2000; 275: 1521–1524.

    Article  CAS  PubMed  Google Scholar 

  24. Tsopanoglou NE, Maragoudakis ME . On the mechanism of thrombin-induced angiogenesis. Potentiation of vascular endothelial growth factor activity on endothelial cells by up-regulation of its receptors. J Biol Chem 1999; 274: 23969–23976.

    Article  CAS  PubMed  Google Scholar 

  25. 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: 8663–8668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ott I, Fischer E, Miyagi Y, Mueller BM, Ruf W . A role for TF in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140: 1241–1253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Belting M, Dorrel MI, Sandgren S, Aguilar E, Ahamed J, Dorfleutner A et al. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nat Med 2004; 10: 502–509.

    Article  CAS  PubMed  Google Scholar 

  28. Hjortoe GM, Petersen LC, Albrektsen T, Sorensen BB, Norby PL, Mandal SK et al. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. Blood 2004; 103: 3029–3037.

    Article  CAS  PubMed  Google Scholar 

  29. Camerer E, Huang W, Coughlin SR . Tissue factor and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000; 97: 5255–5260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Riewald M, Ruf W . Mechanistic couple of protease signaling and initiation of coagulation by tissue factor. Proc Natl Acad Sci USA 2001; 98: 7742–7747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ahamed J, Ruf W . Protease-activated receptor 2-dependent phosphorylation of the tissue factor cytoplasmic domain. J Biol Chem 2004; 279: 23038–23044.

    Article  CAS  PubMed  Google Scholar 

  32. Riewald M, Krawchenko VV, Petrovan RJ, O’Brien PJ, Brass LF, Ulevitch RJ et al. Gene induction by coagulation factor Xa is mediated by activation of protease-activated receptor 1. Blood 2001; 97: 3109–3116.

    Article  CAS  PubMed  Google Scholar 

  33. Rickes FR, Hair GA, Zeff RA, Lee E, Bona RD . Tissue Factor expression in human leukocytes and tumor cells. Thromb Haemost 1995; 74: 391–395.

    Google Scholar 

  34. Cantero D, Friess H, Deflorin J, Zimmermann A, Brundler MA, Riesle E et al. Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br J Cancer 1997; 75: 388–395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bromberg ME, Sundaram R, Homer RJ, Garen A, Konisgsberg WH . Role of TF in metastasis functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost 1999; 82: 88–92.

    Article  CAS  PubMed  Google Scholar 

  36. Wang H, Fu W, Im JH, Zhou Z, Santoro SA, Iyer V et al. Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol 2004; 164: 935–941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dorfleutner A, Hintermann E, Tarui T, Takada Y, Ruf W . Crosstalk of integrin alpha-3,1 and tissue factor in cell migration. Mol Biol Cell 2004; 15: 4416–4425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pérez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J . Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 1997; 150: 815–821.

    PubMed  PubMed Central  Google Scholar 

  39. Hussong JW, Rodgers GM, Shami PJ . Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood 2000; 95: 309–313.

    CAS  PubMed  Google Scholar 

  40. Aguayo A, Kantarjian H, Manshouri T, Gidel G, Estey E, Thomas D et al. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000; 96: 2240–2245.

    CAS  PubMed  Google Scholar 

  41. Lundberg LG, Lerner R, Sundelin P, Rogers R, Folkman J, Palmblad J . Bone marrow polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity. Am J Pathol 2000; 157: 15–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vacca A, Ribatti D, Roncali L, Dammacco F . Angiogenesis in B cell lymphoproliferative diseases: biological and clinical studies. Leukemia Lymphoma 1995; 20: 27–38.

    Article  CAS  PubMed  Google Scholar 

  43. Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF et al. Angiogenesis in myelodysplastic syndromes. Br J Cancer 1999; 81: 1398–1401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood 1999; 93: 3064–3073.

    CAS  PubMed  Google Scholar 

  45. Moehler TM, Hillengass J, Goldschmidt H, Ho AD . Antiangiogenic therapy in hematologic malignancies. Curr Pharm Des 2004; 10: 1221–1234.

    Article  CAS  PubMed  Google Scholar 

  46. Bergers G, Benjamin LE . Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003; 3: 401–410.

    Article  CAS  PubMed  Google Scholar 

  47. Podar K, Anderson KC . The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood 2005; 105: 1383–1395.

    Article  CAS  PubMed  Google Scholar 

  48. Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T et al. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood 2001; 98: 428–435.

    Article  CAS  PubMed  Google Scholar 

  49. Kini AR, Peterson LC, Tallman MS, Lingen MW . Angiogenesis in acute promyelocytic leukemia: induction by VEGF and inhibition by all-trans retinoic acid. Blood 2001; 97: 3919–3924.

    Article  CAS  PubMed  Google Scholar 

  50. Dias S, Shmelkov SV, Lam G, Rafii S . VEGF(165) promotes survival of leukemic cells by Hsp-90-mediated induction of Bcl-2 expression and apoptosis inhibition. Blood 2002; 99: 2532–2540.

    Article  CAS  PubMed  Google Scholar 

  51. Ria R, Roccaro AM, Merchionne F, Vacca A, Dammacco F, Ribatti D . VEGF and its receptors in multiple myeloma. Leukemia 2003; 17: 1961–1966.

    Article  CAS  PubMed  Google Scholar 

  52. List AF . Vascular endothelial growth factor signaling pathway as an emerging target in hematologic malignancies. Oncologist 2001; 6: 24–31.

    Article  CAS  PubMed  Google Scholar 

  53. Gerber HP, Malik AK, Solar GP, Sherman D, Liang XH, Meng G et al. VEGF regulates hematopoietic stem cell survival by an internal autocrine loop mechanism. Nature 2002; 417: 954–958.

    Article  CAS  PubMed  Google Scholar 

  54. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S et al. Production of VEGF by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996; 2: 1096–1103.

    Article  CAS  PubMed  Google Scholar 

  55. Nakagawa M, Kaneda T, Arakawa T, Morita S, Sato T, Yomada T et al. Vascular endothelial growth factor (VEGF) directly enhances osteoclastic bone resorption and survival of mature osteoclasts. FEBBS lett 2000; 473: 161–164.

    Article  CAS  Google Scholar 

  56. Henriksen K, Karsdal M, Delaisse JM, Engsig MT . RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through and ERK1/2 dependent mechanism. J Biol Chem 2003; 278: 48745–48753.

    Article  CAS  PubMed  Google Scholar 

  57. Hanahan D, Weinberg RA . The hallmarks of cancer. Cell 2000; 100: 57–70.

    Article  CAS  PubMed  Google Scholar 

  58. Lee JT, McCubrey JA . The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia. Leukemia 2002; 16: 486–507.

    Article  CAS  PubMed  Google Scholar 

  59. Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA . JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BRC-ABL in cell cycle progression and leukemogenesis. Leukemia 2004; 18: 189–218.

    Article  CAS  PubMed  Google Scholar 

  60. Rak J, Yu JL, Klement G, Kerbel RS . Oncogenes and angiogenesis: signaling three-dimensional tumor growth? J Invest Dermatol Symp Proc 2000; 5: 24–33.

    Article  CAS  Google Scholar 

  61. 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: 376–383.

    Article  CAS  PubMed  Google Scholar 

  62. Oeth P, Parry GC, Mackman N . Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NFkappaB/Rel, and SP1 proteins in uninduced and lipopolysaccharide-induced expression. Arterioscler Thromb Vasc Biol 1997; 17: 365–374.

    Article  CAS  PubMed  Google Scholar 

  63. Birkenkamp KU, Geugien M, Schepers H, Westra J, Lemmink HH, Vellenga E . Constitutive NFkappaB DNA-binding activity in AMLs is frequently mediated by Ras/PI3K/PKB-dependent pathway. Leukemia 2004; 18: 103–112.

    Article  CAS  PubMed  Google Scholar 

  64. Lu T, Sathe SS, Swiatkowski SM, Hampole CV, Stark GR . Secretion of cytokines and growth factors as a general cause of constitutive NFkappaB activation in cancer. Oncogene 2004; 23: 2138–2145.

    Article  CAS  PubMed  Google Scholar 

  65. Mano H . Stratification of acute myeloid leukemia based on gene expression profiles. Int J Hematol 2004; 80: 389–394.

    Article  CAS  PubMed  Google Scholar 

  66. Smith DL, Evans CA, Pierce A, Gaskell SJ, Whetton AD . Changes in the proteasome associated with the action of Brc-Abl tyrosine kinase are not related to transcriptional regulation. Mol Cell Proteomics 2002; 11: 876–884.

    Article  CAS  Google Scholar 

  67. Behre G, Reddy VA, Tenen DG, Hiddemann W, Zada AA, Singh SM . Proteomic analysis of transcription factor interactions in myeloid stem cell development and leukemia. Expert Opin Ther Targets 2002; 6: 491–495.

    Article  CAS  PubMed  Google Scholar 

  68. Seong JK, Kim do K, Choi KH, Oh SH, Kim KS, Lee SS et al. Proteomic analysis of the cellular proteins induced by adaptive concentrations of hydrogen peroxide in human U937 cells. Exp Mol Med 2002; 34: 374–378.

    Article  CAS  PubMed  Google Scholar 

  69. Harris HN, Ozpolat B, Abdi F, Gu S, Legler A, Mawuenyega KG et al. Comparative proteomic analysis of all-trans retinoic acid treatment reveals systematic posttranscriptional control mechanisms in acute promyelocytic leukemia. Blood 2004; 104: 1314–1323.

    Article  CAS  PubMed  Google Scholar 

  70. García-Echevarría C, Pearson MA, Hofmann F, Anderson KC, Kung AL . Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell 2004; 5: 221–230.

    Article  Google Scholar 

  71. López-Pedrera CH, Villalba JM, Siendones E, Barbarroja N, Gómez-Díaz C, Rodríguez-Ariza A et al. Proteomic analysis of acute myeloid leukemia: identification of potential early biomarkers and therapeutic targets. Proteomics 2006; Suppl 1: S293–S299.

  72. Hachiya M, Akashi M . Catalase regulates cell growth in HL60 human promyelocytic cells: evidence for growth regulation by H2O2 . Radiat Res 2005; 163: 271–282.

    Article  CAS  PubMed  Google Scholar 

  73. Aldridge LC, Harris HJ, Plevin R, Hannon R, Bryant CE . The annexin protein lipocortin I regulates the MAPK/ERK pathway. J Biol Chem 1999; 274: 37620–37628.

    Article  Google Scholar 

  74. Shah V, Braverman R, Prasad GL . Suppression of neoplastic transformation and regulation of cytoskeleton by tropomyosins. Somat Cell Mol Genet 1998; 24: 273–280.

    Article  CAS  PubMed  Google Scholar 

  75. Hu Z, Garen A . Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancers. Proc Natl Acad Sci USA 2001; 98: 12180–12185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nilsson F, Kosmehl H, Zardi L, Neri D . Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. Cancer Res 2001; 61: 711–716.

    CAS  PubMed  Google Scholar 

  77. Moehler TM, Neben K, Ho AD, Goldschmidt H . Angiogenesis in hematologic malignancies. Ann Hematol 2001; 80: 695–705.

    Article  CAS  PubMed  Google Scholar 

  78. O’Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003; 101: 3597–3605.

    Article  CAS  PubMed  Google Scholar 

  79. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targetins vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003; 9: 327–337.

    CAS  PubMed  Google Scholar 

  80. Fiedler W, Serve H, Döhner H, Shwittay M, Ottmann OG, O’Farrel AM et al. A phase I study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for disease. Blood 2005; 105: 986–993.

    Article  CAS  PubMed  Google Scholar 

  81. Prentice HG, Sacchi S, Russel N . Future directions in hematology: beyond multiple myeloma. Acta Hematol 2005; 114: 27–32.

    Article  Google Scholar 

  82. Zangari M, Siegel E, Barlogie B, Anaissie E, Saghafifar F, Fassas A et al. Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 2002; 100: 1168–1171.

    Article  CAS  PubMed  Google Scholar 

  83. Kuenen BC, Rosen L, Smith EF, Parson MR, Levi M, Ruijter R et al. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 2002; 20: 1657–1667.

    Article  CAS  PubMed  Google Scholar 

  84. Gorin NC, Estey E, Jones RJ, Levitsky HI, Borrello I, Slavin S . New developments in the therapy of acute myelocytic leukemia. Hematology (Am Soc Hematol Educ Program) 2000, 69–89.

  85. López-Pedrera CH, Dobado-Berrios PM, Ros R, Torres A, García-Navarro S, Jardí M et al. Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in differentiating promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP. Thromb Haemost 2001; 85: 1031–1036.

    Article  PubMed  Google Scholar 

  86. López-Pedrera CH, Barbarroja N, Buendia Bello P, Torres A, Dorado G, Velasco F . Promyelocytic leukemia retinoid signaling targets regulate apoptosis, tissue factor and thrombomodulin expression. Haematologica 2004; 89: 286–295.

    PubMed  Google Scholar 

  87. Marchetti M, Vignoli A, Bani MA, Balducci D, Barbui T, Falanga A . All-trans retinoic acid modulates microvascular endothelial cell hemostatic properties. Haematologica 2003; 88: 895–905.

    CAS  PubMed  Google Scholar 

  88. Roboz GJ, Dias S, Lam G, Lane WJ, Soignet SL, Varrell RP et al. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert and antileukemic effect via inhibition of angiogenesis. Blood 2000; 96: 1525–1530.

    CAS  PubMed  Google Scholar 

  89. Chen Z, Chen G-Q, Shen Z-X, Chen S-J, Wang Z-Y . Treatment of acute promyelocytic leukemia with arsenic compounds: in vitro and in vivo studies. Semin Hematol 2001; 38: 26–36.

    Article  CAS  PubMed  Google Scholar 

  90. Shen Z-X, Shi Z-Z, Fang J, Gu B-W, Li J-M, Zhu Y-M et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci 2004; 101: 5328–5335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Anderson KC, Boise LH, Louie R, Waxman S . Arsenic trioxide in multiple myeloma: rationale and future directions. Cancer J 2002; 8: 12–25.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

ChLP was supported by a Science and Technology postdoctoral contract. This work was supported by grants from the ‘Fondo de Investigación Sanitaria’ (FIS PI041291 and PI050910) and Junta de Andalucia (0024/2005 and 0060/2005) of Spain.

Author information

Authors and Affiliations

  1. Unidad de Investigación, Hospital Universitario Reina Sofía, Córdoba, Spain

    C López-Pedrera, N Barbarroja, E Siendones & F Velasco

  2. Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, Córdoba, Spain

    G Dorado

Authors
  1. C López-Pedrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Barbarroja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Dorado
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Siendones
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C López-Pedrera.

Rights and permissions

Reprints and permissions

About this article

Cite this article

López-Pedrera, C., Barbarroja, N., Dorado, G. et al. Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies. Leukemia 20, 1331–1340 (2006). https://doi.org/10.1038/sj.leu.2404264

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404264

Keywords

This article is cited by

Search

Advanced search

Quick links