Skip to main content
SpringerLink
Log in

The Role of Thrombin in Tumor Biology

  • Chapter
  • First Online:
Thrombin

Abstract

A large body of work supports the association of thrombosis and malignancy. Accumulating laboratory and clinical data point to the important role of thrombin in tumor biology. Thrombin is able to stimulate tumor adhesion and growth by direct tumor cell activation through membrane protease-activated receptors (PARs) or indirectly through platelet–tumor cell interactions and angiogenesis. Thrombin is able to enhance metastases by increasing tumor cell seeding into the circulation, by platelet-mediated tumor cell sequestration and protection from immune cells, and by stimulating tumor neoangiogenesis. In addition we hypothesize that thrombin may preserve dormant tumor cells in individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arora, P., Cuevas, B.D., Russo, A., Johnson, G.L., and Trejo, J 2008.Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasion. Oncogene 27: 4434–4435.

    Article  PubMed  CAS  Google Scholar 

  • Baggiolini, M., DeWald, B., and Moser, B. 1994. Interleukin-8 and related chemotactic cytokines CXC and CC chemokines. Adv. Immunol. 55: 97–179.

    Article  PubMed  CAS  Google Scholar 

  • Bayko, L., Rak, J., Man, S., Bicknell, R., Ferrara, N., and Kerbel, R.S. 1998. The dormant in vivo. phenotype of early stage primary human melanoma: termination by overexpression of vascular endothelial growth factor Angiogenesis 2: 203–217.

    Article  PubMed  CAS  Google Scholar 

  • Biggerstaff, J.P., Seth, N., Amirkhosravi, A., Amaya, M., Fogarty, S., Meyer, T.V., Siddiqui, F., and Francis, J.L. 1999. Soluble fibrin augments platelet/tumor cell adherence in vitro. and in vivo, and enhances experimental metastasis Clin. Exp. Metastasis 17: 723–730.

    Article  PubMed  CAS  Google Scholar 

  • Boucharaba, A., Serre, C., Gres, S., Saulnier-Blache, J., Bordet, J., Guglielmi, J., Clezardin, P., and Peyruchaud, O. 2004. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J. Clin. Invest. 114: 1714–1725.

    PubMed  CAS  Google Scholar 

  • Boukerche, H., Berthier-Vergnes, O., Tabone, E., Dore, J., Leung, L., and McGregor, J. 1989. Platelet–melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex. Blood 74: 658–663.

    PubMed  CAS  Google Scholar 

  • Brill, A., Elinav, H., and Varon, D. 2004. Differential role of platelet granular mediators in angiogenesis. Cardiovasc. Res. 63: 226–235.

    Article  PubMed  CAS  Google Scholar 

  • Brill, A., Dashevsky, O., Rivo, J., Gozal, Y., and Varon, D. 2005. Platelet derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc. Res. 67: 30–38.

    Article  PubMed  CAS  Google Scholar 

  • Camerer, E., Qazi, A., Duong, D., Cornelissen, I., Rommel, A., and Coughlin, S. 2004. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 104: 397–401.

    Article  PubMed  CAS  Google Scholar 

  • Carney, D., Stiernberg, J., and Fenton, J. 1984. Initiation of proliferative events by human α-thrombin requires both receptor binding and enzymatic activity J. Cell. Biochem.26: 181–195.

    Article  PubMed  CAS  Google Scholar 

  • Caunt, M., Huang, Y., Brooks, P., and Karpatkin, S. 2003. Thrombin induces neoangiogenesis in the chick chorioallantoic membrane. J. Thromb. Haemost. 1: 2097–2102.

    Article  PubMed  CAS  Google Scholar 

  • Caunt, M., Hu, L., Tang, T., Brooks, P., Ibrahim, S., and Karpatkin, S. 2006. Growth-regulated oncogene is pivotal in thrombin-induced angiogenesis. Cancer Res. 66: 4125–4132.

    Article  PubMed  CAS  Google Scholar 

  • Chen, L. and Buchanan, J. 1975. Mitogenic activity of blood components. Thrombin and prothrombin. Proc. Natl. Acad. Sci. USA 72: 131–135.

    Article  PubMed  CAS  Google Scholar 

  • Dardik, R., Savion, N., Kaufmann, Y., and Varon, D. 1998. Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIa. Br. J. Cancer 77: 2069–2075.

    Article  PubMed  CAS  Google Scholar 

  • Devalaraja, R., Nanney, L., Du, J., Qian, Q., Yu, Y., Devalaraja, M.N., and Richmond, A. 2000. Delayed wound healing in CXCR2 knockout mice. J. Invest. Dermatol. 115: 234–244.

    Article  PubMed  CAS  Google Scholar 

  • Even-Ram, S., Uziely, B., Cohen, P., Grisaru-Granovsky, S., Maoz, M., and Fidler, I. 1970. Metastases: quantitative analysis of distribution and fate of tumor emboli labeled with 125I-5-iodo-2′-deoxyuridine. J. Natl. Cancer Inst. 45: 773–782.

    Google Scholar 

  • Gasic, G., Gasic, T., and Stewart, C. 1968. Antimetastatic effects associated with platelet reduction. Proc. Natl. Acad. Sci. USA 61: 46–52.

    Article  PubMed  CAS  Google Scholar 

  • Gasic, G., Gasic, T., Galanti, N., Johnson, T., and Murphy, S. 1973. Platelet tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. Int. J. Cancer 11: 704–718.

    Article  PubMed  CAS  Google Scholar 

  • Geaquinto, D.L.A., Fernandes, R.S., Lima, L.G., Barja-Fidalgo, C., and Monteiro, R.Q. 2008. Procoagulant properties of human MV3 melanoma cells. Brazil. J. Med. Biol. Res. 41: 99–105.

    Article  CAS  Google Scholar 

  • Gospodarowicz, D., Brown, K., Birdwell, C., and Zetter, B. 1978. Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin. J. Cell Biol. 77: 774–788.

    Article  PubMed  CAS  Google Scholar 

  • Hanahan, D. and Weinberg, R.A. 2000. The hallmarks of cancer. Cell 100: 57–70.

    Article  PubMed  CAS  Google Scholar 

  • Harach, H., Franssila, K., and Wasenius, V. 1985. Occult papillary carcinoma of the thyroid: a “normal” finding in Finland. A systematic autopsy study. Cancer 56: 531–538.

    Article  PubMed  CAS  Google Scholar 

  • Haralabopoulos, G., Grant, D., Kleinman, H., and Maragoudakis, M. 1997. Thrombin promotes endothelial cell alignment in Matrigel in vitro. and angiogenesis in vivo Am. J. Physiol. Cell Physiol. 273: C239–C245.

    CAS  Google Scholar 

  • Helland, I., Klemensten, B., and Jorgensen, L. 1997. Addition of both platelets and thrombin in combination accelerates tumor cells to adhere to endothelial cells in vitro. In Vitro Cell. Dev. Biol. 33: 182–186.

    Article  Google Scholar 

  • Hu, L., Lee, M., Campbell, W., Perez-Soler, R., and Karpatkin, S. 2004. Role of endogenous thrombin in tumor implantation, seeding and spontaneous metastasis. Blood 104: 2746–2751.

    Article  PubMed  CAS  Google Scholar 

  • Hu, L., Roth, J.M., Broales, P., Ibrahim, S., and Karpatkin, S. 2008.Twist is required for thrombin-induced tissue tumor angiogenesis and growth. Cancer Res. 68: 4296–4302.

    Article  PubMed  CAS  Google Scholar 

  • Huang, Y.Q., Li, J.-J., Hu, L., and Karpatkin, S. 2000. Thrombin induces the synthesis of VEGF and Angiopoietin-2 (Ang-2). Blood 96: 34A.

    Google Scholar 

  • Huang, Y., Li, J., Hu, L., Lee, M., and Karpatkin, S. 2002. Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells. Blood 99: 1646–1650.

    Article  PubMed  CAS  Google Scholar 

  • Humphries, M., Olden, K., and Yamada, K. 1986. A synthetic peptide from fibronectin inhibits experimental metastases of murine melanoma cells. Science 467: 467–470.

    Article  Google Scholar 

  • Humphries, M., Olden, K., and Yamada, K. 1988. Investigation of the biological effect of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16F10 murine melanoma cells. J. Clin. Invest. 81: 782–790.

    Article  PubMed  CAS  Google Scholar 

  • Iwamoto, Y., Robey, F., and Graf, J. 1987. YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science 238: 1132–1134.

    Article  PubMed  CAS  Google Scholar 

  • Jones, J., Wallace, A., and Fraser, E. 1971. Sequence of events in experimental and electron microscopic observations. J. Natl. Cancer Inst. 46: 493–504.

    PubMed  CAS  Google Scholar 

  • Kakkar, A.K., Levine, M.N., Kadziola, Z., Lemoine, N.R., Low, V., Patel, H.K., Rustin, G., Thomas, M., Quigley, M., and Williamson, R.C. 2004. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J. Clin. Oncol. 22: 1944–1948.

    Article  PubMed  CAS  Google Scholar 

  • Karpatkin, S., Ambrogio, C., and Pearlstein, E. 1984. Lack of effect of in vivo. prostacyclin on the development of pulmonary metastases in mice following intravenous injection of CT26 colon carcinoma, Lewis lung carcinoma, or B16 amelanotic melanoma cells Cancer Res. 44: 3880–3883.

    PubMed  CAS  Google Scholar 

  • Karpatkin, S., Pearlstein, E., Ambrogio, C., and Coller, B. 1988. Role of adhesive proteins in platelet tumor interaction in vitro. and metastasis formation in vivo J. Clin. Invest. 81: 1012–1019.

    Article  PubMed  CAS  Google Scholar 

  • Keane, M., Belperio, J., Xue, Y., Burdick, M., and Strieter, R. 2004. Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J. Immunol. 172: 2853–2860.

    PubMed  CAS  Google Scholar 

  • Kepner, N. and Lipton, A. 1981. A mitogenic factor for transformed fibroblasts from human platelets. Cancer Res. 41: 430–432.

    PubMed  CAS  Google Scholar 

  • Kim, Y., Borsig, L., Varki, N., and Varki, A. 1998. P-selectin deficiency attenuates tumor growth and metastasis. Proc. Natl. Acad. Sci. USA 95: 9325–9330.

    Article  PubMed  CAS  Google Scholar 

  • Klepfish, A., Greco, M., and Karpatkin, S. 1993. Thrombin stimulates melanoma tumor-cell binding to endothelial cells and subendothelial matrix. Int. J.Cancer 53: 978–982.

    Article  PubMed  CAS  Google Scholar 

  • Konety, B., Bird, V., Deorah, S., and Dahmoush, L. 2005. Comparison of the incidence of latent prostate cancer detected at autopsy before and after the prostate specific antigen era. J. Urol. 174: 1785–1788.

    Article  PubMed  Google Scholar 

  • Konstantoulaki, M., Kouklis, P., and Malik, A. 2003. Protein kinase C modifications of VE-cadherin, p120, and β-catenin contribute to endothelial barrier dysregulation induced by thrombin. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L434–L442.

    PubMed  CAS  Google Scholar 

  • Kwon, H.-C., Oh, S.L., Kim, S.-H., Han, J.Y., Koh, R.Y., Kim, M.C., and Kim, H.-J. 2008. Plasma levels of prothrombin fragment F112, D-dimer and prothrombin time correlate with clinical stage and lymph node metastasis in operable gastric cancer patients. Jpn. J. Clin. Oncol. 38: 2–7.

    Article  PubMed  Google Scholar 

  • Kyle, R. 1997. Monoclonal gammopathy of undetermined significance and solitary myeloma. Hematol. Oncol. Clin. North Am. 11: 71–87.

    Article  PubMed  CAS  Google Scholar 

  • Langer, F., Amirkhosravi, A., Ingersoll, S.B., Walker, J.M., Spath, B., Eifrig, B., Bokemeyer, C., and Francis, J.L. 2006. Experimental metastasis and primary tumor growth in mice with hemophilia A. J. Thromb. Haemost. 4:1056–1062.

    Article  PubMed  CAS  Google Scholar 

  • Lazo-Langner, A., Goss, G.D., Spaans, J.N., and Rodger, M.A. 2007. The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J. Thromb. Haemost. 5: 729–737.

    Article  PubMed  CAS  Google Scholar 

  • Levitan, N., Dowlati, A., Remick, S.C. et al. 1999. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine : 78285–291.

    Article  CAS  Google Scholar 

  • Li, J.-J., Huang, Y.-Q., Basch, R., and Karpatkin, S. 2001. Thrombin induces the release of angiopoietin-1 from platelets. Thromb. Haemost. 85: 204–206.

    PubMed  CAS  Google Scholar 

  • Liao, F., Li, Y., O’Connor, W., Zanetta, L., Bassi, R., Santiago, A., Overholster, J., Hooper, A., Mignatti, P., Dejana, E., et al. 2000. Monoclonal antibody to VE-cadherin is a potent inhibitor to angiogenesis, tumor growth and metastasis. Cancer Res. 60: 6805–6812.

    PubMed  CAS  Google Scholar 

  • Loukinova, E., Dong, G., Enamorado-Ayalya, I., Thomas, G.R., Chen, Z., Schreiber, H., and Van Waes, C. 2000. Growth regulated oncogene-a expression bymurine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC Receptor-2 dependent mechanism. Oncogene 19: 3477–3486.

    Article  PubMed  CAS  Google Scholar 

  • MacKie, R., Reid, R., and Junor, B. 2003. Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery N. Engl. J. Med. 348: 567–568.

    Article  PubMed  Google Scholar 

  • Martin, C., Mahon, G., Klinger, M., Kay, R., Symons, M., Der, C., and Whitehead, I. 2001. The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways. Oncogene 20: 1953–1963.

    Article  PubMed  CAS  Google Scholar 

  • McCarty, O., Mousa, S., Bray, P., and Konstantopoulos, K. 2000. Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. Blood 96: 1789–1797.

    PubMed  CAS  Google Scholar 

  • McGregor, B., McGregor, J., Weiss, L., Wood, G., Hu, C., Boukerche, H., and Warnke, R.A. 1989. Presence of cytoadhesins (IIb-IIIa-like glycoproteins) on human metastatic melanomas but not on benign melanocytes. Am. J. Clin. Pathol. 92: 495–499.

    PubMed  CAS  Google Scholar 

  • Miller, G., Bauer, K., Howarth, D., Cooper, J., Humphries, S., and Rosenberg, R. 2004. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway. J. Thromb. Haemost. 2: 2107–2114.

    Article  PubMed  CAS  Google Scholar 

  • Mohle, R., Green, D., Moore, M., Nachman, R., and Rafii, S. 1997. Constitutive production and thrombin-induced release of VEGF by human megakaryocytes and platelets. Proc. Natl. Acad. Sci. USA 94: 663–668.

    Article  PubMed  CAS  Google Scholar 

  • Nielsen, M., Thomsen, J., Primdahl, S., Dyreborg, U., and Andersen, J. 1987. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br. J. Cancer 56: 814–819.

    Article  PubMed  CAS  Google Scholar 

  • Nierodzik, M.L. and Karpatkin, S. 2006. Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10: 355–362.

    Article  PubMed  CAS  Google Scholar 

  • Nierodzik, M., Plotkin, A., Kajumo, F., and Karpatkin, S. 1991. Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.. J Clin. Invest. 87: 229–236.

    Article  CAS  Google Scholar 

  • Nierodzik, M., Kajumo, F., and Karpatkin, S. 1992. Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro. and metastasis in vivo Cancer Res. 52: 3267–3272.

    PubMed  CAS  Google Scholar 

  • Nierodzik, M., Bain, R., Liu, L.-X., Shivji, M., Takeshita, K., and Karpatkin, S. 1996. Presence of the seven transmembrane thrombin receptor on human tumour cells: effect of activation on tumour adhesion to platelets and tumour tyrosine phosphorylation. Br. J. Haematol. 92: 452–457.

    Article  PubMed  CAS  Google Scholar 

  • Nierodzik, M., Chen, K., Takeshita, K., Li, J., Huang, Y., Feng, X., D’Andrea, M., Andrade-Gordon, P., and Karpatkin, S. 1998. Protease-activated receptor 1 (PAR-1) is required and rate-limiting for thrombin-enhanced experimental pulmonary metastasis. Blood 92: 3694–3700.

    PubMed  CAS  Google Scholar 

  • Nieswandt, B., Hafner, M., Echtenacher, B., and Mannel, D. 1999. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 59: 1295–1300.

    PubMed  CAS  Google Scholar 

  • Ollivier, V., Chabbat, J., Herbert, J.M., Hakim, J., and de Prost, D. 2000. 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. 20: 1374–1381.

    Article  PubMed  CAS  Google Scholar 

  • Palumbo, J.S., Talmage, K.E., Massari, J.V., La Jeunesse, C.M., Flick, M.J., Kombrinck, K.W., Jirouskova, M., and Degen, J.L. 2005. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105: 178–185.

    Article  PubMed  CAS  Google Scholar 

  • Prandoni, P., Lensing, A.W., Buller, H.R., Cogo, A., Prins, M.H., Cattelan, A.M., Cuppini, S., Noventa, F., Ten Cate, J.W. 1992. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N. Engl. J. Med. 327: 1128–1133.

    Article  PubMed  CAS  Google Scholar 

  • Radjabi, A.R., Sawada, K., Jagadeeswaran, S., Eichbichler, A., Kenny, H.A., Montag, A., Bruno, K., and Lengyel, E. 2008. Thrombin induces tumor invasion through the induction and association of matrix metalloproteinase-9 and-1-integrin on the cell surface. J. Biol. Chem. 283: 2822–2834.

    Article  PubMed  CAS  Google Scholar 

  • Rawstron, A., Yuille, M., Fuller, J., Cullen, M., Kennedy, B., Richards, S., Jack, A., Matutes, E., Catovsky, D., Hillmen, P., and Houlston, R. 2002. Inherited predisposition to CLL is detectable as a subclinical monoclonal B-lymphocyte expansion. Blood 100: 2289–2290.

    Article  PubMed  CAS  Google Scholar 

  • Schulze, E.B., Hedley, B.D., Goodale, D., Postenka, C.O., Al-Katib, W.A., Tuck, A.B., Chambers, A.F., and Allan, A.L. The thrombin inhibitor Argatroban reduces breast cancer malignancy and metastasis via osteopontin-dependent and osteopontin-independent mechanisms. Breast Cancer Res Treat (in press).

    Google Scholar 

  • Shulman, S. and Lindmarker, P. 2000. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of anticoagulation trial. N. Engl. J. Med. 342: 1953–1958.

    Article  Google Scholar 

  • Sorensen, H.T., Mellemkjaer, L., Steffensen, F.H., Olsen, J.H., and Nielsen, G.L. 1998. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N. Engl. J. Med. 338: 1169–1173.

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, H.T., Mellemkjaer, L., Olsen, J.H., and Baron, J.A. 2000. Prognosis of cancers associated with venous thromboembolism. N. Engl. J. Med. 343: 1846–1850.

    Article  PubMed  CAS  Google Scholar 

  • Stein, W.D. and Litman, T. 2006. Data on the recurrence of breast tumors fit a model in which dormant cells are subject to slow attrition but can randomly awaken to become malignant. Cell Cycle 5: 2348–2353.

    Article  PubMed  CAS  Google Scholar 

  • Stevenson, J., Choi, S., and Varki, A. 2005. Differential metastasis inhibition by clinically relevant levels of heparins. Correlation with selectin inhibition, not antithrombotic activity. Clin. Cancer Res. 11: 7003–7011.

    Article  PubMed  CAS  Google Scholar 

  • Strieter, R.M., Burdick, B.M., Gomports, B.N., Belperio, J.A., and Keane, M.P. 2005. C-X-C chemokines in angiogenesis. Cytokine Growth Factor Rev. 16: 593–609.

    Article  PubMed  CAS  Google Scholar 

  • Svendsen, E. and Karwinski, B. 1989. Prevalence of pulmonary embolism at necropsy in patients with cancer. J. Clin. Pathol. 42: 805–809

    Article  PubMed  CAS  Google Scholar 

  • Trousseau, A. 1865. Phlegmasia alba dolens. New Sydenham Society. London: 281–295.In: Lectures on clinical medicine.

    Google Scholar 

  • Tsopanoglou, N. and Maragoudakis, M. 1999. 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. 274: 23969–23976.

    Article  PubMed  CAS  Google Scholar 

  • Versteeg, H.H., Schaffner, F., Kerver, M., Petersen, H.H., Ahamed, J., Felding-Habermann, B., Takada, Y., Mueller, B.M., and Ruf, W. 2008. Inhibition of tissue factor signaling suppresses tumor growth. Blood 111: 190–199.

    Article  PubMed  CAS  Google Scholar 

  • Yang, J., Mani, S., Donaher, J., Ramaswamy, S., Itzykson, R., Come, C., Savagner, P., Gitelman, I., Richardson, A., and Weinberg, R. 2004. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117: 927–939.

    Article  PubMed  CAS  Google Scholar 

  • Zacharski, L., Memoli, V., Morain, W., Schlaeppi, J.-M., and Rousseau, S. 1995. Cellular localization of enzymatically-active thrombin in intact tissue by hirudin binding. Thromb. Haemost. 73: 793–797.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine/Hematology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA

    Boris Kobrinsky* & Simon Karpatkin*

Authors
  1. Boris Kobrinsky*
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon Karpatkin*
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boris Kobrinsky* .

Editor information

Editors and Affiliations

  1. Medical School, University of Patras, Patras, Greece

    Michael E. Maragoudakis  & Nikos E. Tsopanoglou  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Kobrinsky*, B., Karpatkin*, S. (2009). The Role of Thrombin in Tumor Biology. In: Maragoudakis, M., Tsopanoglou, N. (eds) Thrombin. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09637-7_9

Download citation

Publish with us

Policies and ethics

Search

Navigation