The role of activated protein C in cancer progression

Thrombosis Research

Volumn 125, Issue , 2010, Pages S138-S142

  van Sluis, Geerte L ^a   Büller, Harry R ^a   Spek, C Arnold ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

Activated protein; C Cancer progression

Indexed keywords

ANTICOAGULANT AGENT; PROTEIN C;

ANIMAL; BLOOD; BLOOD CLOTTING; HUMAN; METABOLISM; METASTASIS; NEOPLASM; REVIEW;

ANIMALS; ANTICOAGULANTS; BLOOD COAGULATION; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; PROTEIN C;

EID: 77955491147     PISSN: 00493848     EISSN: 18792472     Source Type: Journal    
DOI: 10.1016/S0049-3848(10)70032-3     Document Type: Article

References (73)

1. Bouillaud. De l'Obliteration des veines et de son influence sur la formation des hydropisies partielles: consideration sur la hydropisies passive et general. Archives generales de medicine 1 (1823), 188–204.
2. Trousseau A. Phlegmasia alba dolens. In: Peter M, ed. Clinique Medicinale de l'Hotel-Dieu de Paris. 1877: 695–739.
3. Buller, HR, van Doormaal, FF, van Sluis, GL, Kamphuisen, PW, Cancer and thrombosis: from molecular mechanisms to clinical presentations. J Thromb Haemost 5:Suppl 1 (2007), 246–254.
4. Varki, A, Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood 110:6 (2007), 1723–1729.
5. Chew, HK, Wun, T, Harvey, D, Zhou, H, et al. Incidence of Venous Thromboembolism and Its Effect on Survival Among Patients With Common Cancers. Archives of Internal Medicine 166:4 (2006), 458–464.
6. Blom, JW, Doggen, CJM, Osanto, S, Rosendaal, FR, Malignancies, Prothrombotic Mutations, and the Risk of Venous Thrombosis. JAMA 293:6 (2005), 715–722.
7. Carrier, M, Le, GG, Wells, PS, Fergusson, D, et al. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism?. Annals of Internal Medicine 149:5 (2008), 323–333.
8. Akl, EA, van Doormaal, FF, Barba, M, Kamath, G, et al. Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation. Cochrane Database Syst Rev(3), 2007 CD006652.
9. Hettiarachchi, RJ, Smorenburg, SM, Ginsberg, J, Levine, M, et al. Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost 82:2 (1999), 947–952.
10. Akl, EA, Rohilla, S, Barba, M, Sperati, F, et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev(1), 2008 CD006649.
11. Altinbas, M, Coskun, HS, Er, O, Ozkan, M, et al. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost 2:8 (2004), 1266–1271.
12. Kakkar, AK, Levine, MN, Kadziola, Z, Lemoine, NR, et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 22:10 (2004), 1944–1948.
13. Klerk, CPW, Smorenburg, SM, Otten, HM, Lensing, AWA, et al. The Effect of Low Molecular Weight Heparin on Survival in Patients With Advanced Malignancy. J Clin Oncol 23:10 (2005), 2130–2135.
14. Nierodzik, ML, Kajumo, F, Karpatkin, S, Effect of Thrombin Treatment of Tumor Cells on Adhesion of Tumor Cells to Platelets in Vitro and Tumor Metastasis in Vivo. Cancer Research 52:12 (1992), 3267–3272.
15. Nierodzik, ML, Plotkin, A, Kajumo, F, Karpatkin, S, Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. J Clin Investigation 87:1 (1991), 229–236.
16. Huang, YQ, Li, JJ, Hu, L, Lee, M, et al. Thrombin induces increased expression and secretion of VEGF from human FS4 fibroblasts, DU145 prostate cells and CHRF megakaryocytes. Thromb Haemost 86:4 (2001), 1094–1098.
17. Haralabopoulos, GC, Grant, DS, Kleinman, HK, Maragoudakis, ME, Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo. Am J Physiol 273:1 Pt 1 (1997), C239–C245.
18. Hu, L, Lee, M, Campbell, W, Perez-Soler, R, et al. Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis. Blood 104:9 (2004), 2746–2751.
19. Amirkhosravi, A, Mousa, SA, Amaya, M, Francis, JL, Antimetastatic effect of tinzaparin, a low-molecular-weight heparin. J Thromb Haemost 1:9 (2003), 1972–1976.
20. Miao, HQ, Elkin, M, Aingorn, E, Ishai-Michaeli, R, et al. Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides. Int J Cancer 83:3 (1999), 424–431.
21. Stevenson, JL, Choi, SH, Varki, A, Differential metastasis inhibition by clinically relevant levels of heparins – correlation with selectin inhibition, not antithrombotic activity. Clin Cancer Res 11:19 Pt 1 (2005), 7003–7011.
22. Bruggemann, LW, Versteeg, HH, Niers, TM, Reitsma, PH, et al. Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders. J Cell Mol Med 12:6B (2008), 2622–2627.
23. Esmon, CT, The Protein C Pathway. Chest 124:90030 (2003), 26S–232.
24. Conway, EM, Rosenberg, RD, Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Molecular and Cellular Biology 8:12 (1988), 5588–5592.
25. Branson, HE, Katz, J, Marble, R, Griffin, JH, Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 2:8360 (1983), 1165–1168.
26. Seligsohn, U, Berger, A, Abend, M, Rubin, L, et al. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. The New England Journal of Medicine 310:9 (1984), 559–562.
27. Marlar, RA, Montgomery, RR, Broekmans, AW, Report on the diagnosis and treatment of homozygous protein C deficiency. Report of the Working Party on Homozygous Protein C Deficiency of the ICTH-Subcommittee on Protein C and Protein S. Thromb Haemost 61:3 (1989), 529–531.
28. Griffin, JH, Evatt, B, Zimmerman, TS, Kleiss, AJ, et al. Deficiency of protein C in congenital thrombotic disease. J Clin Investigation 68:5 (1981), 1370–1373.
29. Broekmans, AW, Veltkamp, JJ, Bertina, RM, Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families. N Engl J Med 309:6 (1983), 340–344.
30. Allaart, CF, Poort, SR, Rosendaal, FR, Reitsma, PH, et al. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 341:8838 (1993), 134–138.
31. Mewhort-Buist, TA, Liaw, PC, Patel, S, Atkinson, HM, et al. Treatment of endothelium with the chemotherapy agent vincristine affects activated protein C generation to a greater degree in newborn plasma than in adult plasma. Thromb Res 122:3 (2008), 418–426.
32. Woodley-Cook, J, Shin, LYY, Swystun, L, Caruso, S, et al. Effects of the chemotherapeutic agent doxorubicin on the protein C anticoagulant pathway. Molecular Cancer Therapeutics 5:12 (2006), 3303–3311.
33. Feffer, SE, Carmosino, LS, Fox, RL, Acquired protein C deficiency in patients with breast cancer receiving cyclophosphamide, methotrexate, and 5-fluorouracil. Cancer 63:7 (1989), 1303–1307.
34. Rogers, JS, Murgo, AJ, Fontana, JA, Raich, PC, Chemotherapy for breast cancer decreases plasma protein C and protein S. J Clin Oncol 6:2 (1988), 276–281.
35. Feffer, SE, Carmosino, LS, Fox, RL, Acquired protein C deficiency in patients with breast cancer receiving cyclophosphamide, methotrexate, and 5-fluorouracil. Cancer 63:7 (1989), 1303–1307.
36. Lindahl, AK, Boffa, MC, Abildgaard, U, Increased plasma thrombomodulin in cancer patients. Thromb Haemost 69:2 (1993), 112–114.
37. Hanly, AM, Redmond, M, Winter, DC, Brophy, S, et al. Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival. Br J Cancer 94:9 (2006), 1320–1325.
38. Hanly, AM, Winter, DC, The role of thrombomodulin in malignancy. Semin Thromb Hemost 33:7 (2007), 673–679.
39. Higuchi, T, Nakamura, T, Kakutani, H, Ishii, H, Thrombomodulin suppresses invasiveness of HT1080 tumor cells by reducing plasminogen activation on the cell surface through activation of thrombin-activatable fibrinolysis inhibitor. Biol Pharm Bull 32:2 (2009), 179–185.
40. Matsushita, Y, Yoshiie, K, Imamura, Y, Ogawa, H, et al. A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin-expressing clone – thrombomodulin as a possible candidate for an adhesion molecule of squamous cell carcinoma. Cancer Lett 127:1–2 (1998), 195–201.
41. Kim, SJ, Shiba, E, Ishii, H, Inoue, T, et al. Thrombomodulin is a new biological and prognostic marker for breast cancer: an immunohistochemical study. Anticancer Res 17:3C (1997), 2319–2323.
42. Tsuneyoshi, N, Fukudome, K, Horiguchi, S, Ye, X, et al. Expression and anticoagulant function of the endothelial cell protein C receptor (EPCR) in cancer cell lines. Thromb Haemost 85:2 (2001), 356–361.
43. Bezuhly, M, Cullen, R, Esmon, CT, Morris, SF, et al. Role of activated protein C and its receptor in inhibition of tumor metastasis. Blood 113:14 (2009), 3371–3374.
44. Nijziel, MR, van, OR, Christella, M, Thomassen, LG, et al. Acquired resistance to activated protein C in breast cancer patients. Br J Haematol 120:1 (2003), 117–122.
45. Esmon, C, Do-all receptor takes on coagulation, inflammation. Nat Med 11:5 (2005), 475–477.
46. Riewald, M, Schuepbach, RA, Protective Signaling Pathways of Activated Protein C in Endothelial Cells. Arteriosclerosis, Thrombosis, and Vascular Biology 28:1 (2008), 1–3.
47. Schuepbach, RA, Feistritzer, C, Brass, LF, Riewald, M, Activated protein C-cleaved protease activated receptor-1 is retained on the endothelial cell surface even in the presence of thrombin. Blood 111:5 (2008), 2667–2673.
48. Riewald, M, Petrovan, RJ, Donner, A, Ruf, W, Activated protein C signals through the thrombin receptor PAR1 in endothelial cells. J Endotoxin Res 9 (2003), 317–321.
49. Riewald, M, Petrovan, RJ, Donner, A, Mueller, BM, et al. Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway. Science 296:5574 (2002), 1880–1882.
50. Riewald, M, Ruf, W, Protease-activated Receptor-1 Signaling by Activated Protein C in Cytokine-perturbed Endothelial Cells Is Distinct from Thrombin Signaling. J Biol Chem 280:20 (2005), 19808–19814.
51. Bernard, GR, Vincent, JL, Laterre, PF, LaRosa, SP, et al. Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis. N Engl J Med 344:10 (2001), 699–709.
52. Mosnier, LO, Yang, XV, Griffin, JH, Activated Protein C Mutant with Minimal Anticoagulant Activity, Normal Cytoprotective Activity, and Preservation of Thrombin Activable Fibrinolysis Inhibitor-dependent Cytoprotective Functions. J Biol Chem 282:45 (2007), 33022–33033.
53. Kerschen, EJ, Fernandez, JA, Cooley, BC, Yang, XV, et al. Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C. J Exp Med 204:10 (2007), 2439–2448.
54. Feistritzer, C, Riewald, M, Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood 105:8 (2005), 3178–3184.
55. Niessen, F, Furlan-Freguia, C, Fernandez, JA, Mosnier, LO, et al. Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality. Blood 113 (2009), 2859–2866.
56. Ruf, W, PAR1 signaling: more good than harm?. Nat Med 9:3 (2003), 258–260.
57. Uchiba, M, Okajima, K, Oike, Y, Ito, Y, et al. Activated Protein C Induces Endothelial Cell Proliferation by Mitogen-Activated Protein Kinase Activation In Vitro and Angiogenesis In Vivo. Circulation Research 95:1 (2004), 34–41.
58. Beaulieu, LM, Church, FC, Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1. Experimental Cell Research 313:4 (2007), 677–687.
59. Bae, JS, Yang, L, Rezaie, AR, Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cells. Proceedings of the National Academy of Sciences 104:8 (2007), 2867–2872.
60. Joyce, DE, Gelbert, L, Ciaccia, A, DeHoff, B, et al. Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis. Journal of Biological Chemistry 276:14 (2001), 11199–11203.
61. Gramling, MW, Beaulieu, LM, Church, FC, Activated Protein C Enhances Cell Motility of Endothelial Cells and MDA-MB-231 Breast Cancer Cells by Intracellular Signal Transduction. Exp Cell Res, 2009.
62. Cheng, T, Liu, D, Griffin, JH, Fernandez, JA, et al. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 9:3 (2003), 338–342.
63. Guo, H, Liu, D, Gelbard, H, Cheng, T, et al. Activated Protein C Prevents Neuronal Apoptosis via Protease Activated Receptors 1 and 3. Neuron 41:4 (2004), 563–572.
64. O'Brien, LA, Richardson, MA, Mehrbod, SF, Berg, DT, et al. Activated Protein C Decreases Tumor Necrosis Factor Related Apoptosis-Inducing Ligand by an EPCR-Independent Mechanism Involving Egr-1/Erk-1/2 Activation. Arteriosclerosis, Thrombosis, and Vascular Biology 27:12 (2007), 2634–2641.
65. Riewald, M, Schuepbach, RA, Protective Signaling Pathways of Activated Protein C in Endothelial Cells. Arterioscler Thromb Vasc Biol 28:1 (2008), 1–3.
66. Van Sluis, GL, Niers, TMH, Esmon, CT, Tigchelaar, W, et al. Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement. Blood 114:9 (2009), 1968–1973.
67. Feistritzer, C, Schuepbach, RA, Mosnier, LO, Bush, LA, et al. Protective signaling by activated protein C is mechanistically linked to protein C activation on endothelial cells. J Biol Chem 281:29 (2006), 20077–20084.
68. Feistritzer, C, Riewald, M, Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood 105:8 (2005), 3178–3184.
69. Niers, TM, Bruggemann, LW, van Sluis, GL, Liu, RD, et al. Long-term thrombin inhibition promotes cancer cell extravasation in a mouse model of experimental metastasis. J Thromb Haemost 7:9 (2009), 1595–1597.
70. Yamaguchi, H, Kitayama, J, Takuwa, N, Arikawa, K, et al. Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. Biochem J 374:3 (2003), 715–722.
71. Rosen, H, Goetzl, EJ, Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol 5:7 (2005), 560–570.
72. Schmid, G, Guba, M, Ischenko, I, Papyan, A, et al. The immunosuppressant FTY720 inhibits tumor angiogenesis via the sphingosine 1-phosphate receptor 1. J Cell Biochem 101:1 (2007), 259–270.
73. Smorenburg, SM, Vink, R, Otten, HM, Swaneveld, F, et al. The effects of vitamin K-antagonists on survival of patients with malignancy: a systematic analysis. Thromb Haemost 86:6 (2001), 1586–1587.