Download PDF
Thromb Haemost 1989; 62(03): 850-855
DOI: 10.1055/s-0038-1651016
Original Article
Schattauer GmbH Stuttgart

Factors of the Extrinsic Pathway of Blood Coagulation in Tumour Associated Macrophages

Róza Ádány
1   The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
,
János Kappelmayer
1   The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
,
Ernö Berényi
2   IIIrd Department of Medicine, University School of Medicine, Debrecen, Hungary
,
Andrea Szegedi
1   The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
,
Erzsébet Fábián
3   Ist Department of Surgery, University School of Medicine, Debrecen, Hungary
,
László Muszbek
1   The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
› Author Affiliations
Further Information

Publication History

Received 24 January 1989

Accepted after revision 18 May 1989

Publication Date:
30 June 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Despite the growing evidence implicating intratumoural fibrin formation in the progression of malignant tumours, the origin of coagulation factors that participate in extravascular clotting has not been elucidated. Using immunohistochemical methods we attempted to detect and localize clotting factors of extrinsic pathway in different human malignant tumours. Coagulation factors II, V, VII and X (FII, FV, FVII and FX) were detected in a huge number of cells showing spindle-shaped or stellate morphology. By double immunohistochemical labellings it was demonstrated that cells containing these clotting factors express monocyte/macrophage differentiation marker antigens recognized by Leu M3, Ki M7 and DAKO-macrophage monoclonal antibodies, i.e. they represent monocyte-derived, phagocytic tumour associated macrophages (TAMs). These findings suggest that TAMs can be viewed as clot cells, which in addition to the initiation of extravascular clotting by expressing procoagulant activity can also provide all the components necessary for the extrinsic thrombin formation.

Keywords

Macrophages - Intratumoural fibrin formation - Clotting factors
 

  • References

  • 1 Trousseau A. Phlegmasia alba dolens. Clinique Medicale de l'Hotel-Dieu de Paris New Sydenham Society; London: (; 3). 1865: 94
    Google Scholar
  • 2 Rickies FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau's syndrome revisited. Blood 1983; 62: 14-31
    PubMedGoogle Scholar
  • 3 Dvorak HF. Thrombosis and cancer. Hum Pathol 1987; 18: 275-284
    CrossrefPubMedGoogle Scholar
  • 4 Hiromoto R, Bernecky J, Jurandowski J, Pressman D. Fibrin in human tumors. Cancer Res 1960; 20: 592-593
    PubMedGoogle Scholar
  • 5 Chew EC, Wallace AC. Demonstration of fibrin in early stages of experimental metastases. Cancer Res 1976; 36: 1904-1909
    PubMedGoogle Scholar
  • 6 Harris NL, Dvorak AM, Smith J, Dvorak HF. Fibrin deposits in Hodgkin's disease. Am J Pathol 1982; 108: 119-129
    PubMedGoogle Scholar
  • 7 Dvorak HF, Senger DR, Dvorak AM. Fibrin as a component of the tumor stroma: origins and biological significance. Cancer Metast Rev 1983; 2: 41-73
    CrossrefPubMedGoogle Scholar
  • 8 Zacharski LR, Schned A, Sorenson GD. Occurrence of fibrin and tissue factor antigen in small cell carcinoma of the lung. Cancer Res 1983; 43: 3963-3968
    PubMedGoogle Scholar
  • 9 Curatalo L, Colucci M, Cambini AL, Poggi A, Morasca L, Donati MB, Semeraro N. Evidence that cells from experimental tumours can activate coagulant factor X. Br J Cancer 1979; 40: 228-233
    CrossrefPubMedGoogle Scholar
  • 10 Colucci M, Curatalo L, Donati MB, Semeraro N. Cancer cell procoagulant activity: Evaluation by an amidolytic assay. Thromb Res 1980; 18: 589-595
    CrossrefPubMedGoogle Scholar
  • 11 Gordon SG, Franks JJ, Lewis B. Cancer procoagulant A: A factor X activating procoagulant from malignant tissue. Thromb Res 1975; 6: 127-137
    CrossrefPubMedGoogle Scholar
  • 12 Edwards RL, Rickies FR, Cronlund M. Abnormalities of blood coagulation in patients with cancer. Mononuclear cell tissue factor generation. J Lab Clin Med 1981; 98: 917-928
    PubMedGoogle Scholar
  • 13 Viero P, Cortellazzo S, Casarotto C, Barbui T, Colucci M, Semeraro N. Increased production of mononuclear cell procoagulant activity in Hodgkin's disease. Eur J Cancer Clin Oncol 1983; 19: 1539-1543
    CrossrefPubMedGoogle Scholar
  • 14 Lorenzet R, Peri G, Locati D, Allavena P, Colucci M, Semeraro N, Mantovani A, Donati MB. Generation of procoagulant activity by mononuclear phagocytes: a possible mechanism contributing to blood clotting activation within malignant tissues. Blood 1983; 62: 271-273
    PubMedGoogle Scholar
  • 15 Rambaldi A, Alessio G, Casali B, Passerrini CG, Donati MB, Mantovani A, Semeraro N. Induction of monocyte-macrophage procoagulant activity by transformed cell lines. J Immunol 1986; 136: 3848-3855
    PubMedGoogle Scholar
  • 16 Guarini A, Acero R, Alessio G, Donati MB, Semeraro N, Mantovani A. Procoagulant activity of macrophages associated with different murine neoplasms. Int J Cancer 1984; 34: 581-586
    CrossrefPubMedGoogle Scholar
  • 17 Gewirtz AM, Keefer M, Doshi K, Annamalai AE, Chin HC, Colman RW. Biology of human megakaryocyte factor V. Blood 1986; 67: 1639-1648
    PubMedGoogle Scholar
  • 18 Muszbek L, Ádány R, Szegedi G, Polgár J, Kávai M. Factor XIII of blood coagulation in human monocytes. Thromb Res 1985; 37: 401-410
    CrossrefPubMedGoogle Scholar
  • 19 Ádány R, Kappelmayer J, Muszbek L. Expression of FXIII subunit a in different types of human macrophages. Adv Biosci 1987; 69: 778-785
    PubMedGoogle Scholar
  • 20 Dimitriu-Bona A, Burmester GR, Waters SJ, Winchester RJ. Human mononuclear phagocyte differentation antigens. I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol 1983; 130: 145-152
    PubMedGoogle Scholar
  • 21 Kreipe H, Radzun HJ, Parwaresch MR, Haislip A, Hansmann ML. Ki-M7 monoclonal antibody specific for myelomonocytic cell lineage and macrophages in human. J Histochem Cytochem 1987; 35: 1117-1126
    CrossrefPubMedGoogle Scholar
  • 22 Ádány R, Glukhova MA, Kabakov AY, Muszbek L. Characterisation of connective tissue cells containing factor XIII subunit a. J Clin Pathol 1988; 41: 49-56
    CrossrefPubMedGoogle Scholar
  • 23 Iozzo RV. Neoplastic modulation of extracellular matrix. J Biol Chem 1985; 260: 7464-7473
    PubMedGoogle Scholar
  • 24 Martinez-Hernandez A. The extracellular matrix and neoplasia. Lab Invest 1988; 58: 609-612
    PubMedGoogle Scholar
  • 25 Schlager SI, Dray S. Complete local tumor regression with antibody to fibrin fragment E. J Immunol 1975; 115: 976-981
    PubMedGoogle Scholar
  • 26 Donati MB, Mussoni L, Poggi A, deGaetano G, Gerattini S. Growth and metastasis of the Lewis lung carcinoma in mice defibrinated with batroxobin. Eur J Cancer 1978; 14: 343-347
    CrossrefPubMedGoogle Scholar
  • 27 Brown JM. A study of the mechanism by which anticoagulation with warfarin inhibits blood-borne metastases. Cancer Res 1973; 33: 1217-1224
    PubMedGoogle Scholar
  • 28 Zacharski LR. Anticoagulation in the treatment of cancer in man. In: Malignancy and the Hemostatic System. Donati MB, Davidson JF, Garattini S. (eds). Raven Press; New York: 1981: 113-127
  • 29 Schwartz BS, Levy GA, Fair DS, Edgington TS. Murine lymhpoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase. J Exp Med 1982; 155: 1464-1479
    CrossrefPubMedGoogle Scholar
  • 30 Broze Jr GJ. Binding of human factor VII and Vila to monocytes. J Clin Invest 1982; 70: 526-535
    CrossrefPubMedGoogle Scholar
  • 31 Ploplis VA, Edgington TS, Fair DS. Initiation of the extrinsic pathway of coagulation. Association of factor Vila with a cell line expressing tissue factor. J Biol Chem 1987; 262: 9503-9508
    PubMedGoogle Scholar
  • 32 Muszbek L, Laki K. Interaction of thrombin with proteins other than fibrinogen (thrombin susceptible bonds). Activation of factor XIII. In: The Thrombin. Machovich R. (ed). CRC Press; Boca Raton: 1984: 083-102
  • 33 Ádány R, Nemes Z, Thomázy V, Muszbek L. Identification of factor XIII in macrophages invading lymph nodes with Hodgkin's disease. In: Haemostasis and Cancer. Muszbek L. (ed). CRC Press; Boca Raton: 1987: 115-124
  • 34 Ádány R, Nemes Z, Muszbek L. Characterization of factor XIII containing macrophages in lymph nodes with Hodgkin's disease. Br J Cancer 1987; 55: 241-246
    PubMedGoogle Scholar
  • 35 Ádány R, Szegedi A, Ablin RJ, Muszbek L. Fibrinolysis resistant fibrin deposits in lymph nodes with Hodgkin's disease. Thromb Haemostas 1988; 60: 293-297
    PubMedGoogle Scholar
  • 36 Muszbek L, Ádány R. Intratumoral fibrin stabilization. In: Eicosanoids, Lipid Peroxidation and Cancer. Nigam S, McBrien D, Slater T. (eds). Springer-Verlag; Heidelberg: 1988: 339-349
  • 37 Kradin RL, Lynch GW, Kurnick JT, Erikson M, Colvin RB, McDonagh J. Factor XIII is synthetised and expressed on the surface of U937 cells and alveolar macrophages. Blood 1987; 69: 778-785
    PubMedGoogle Scholar
  • 38 Zacharski LR, Memoli VA, Rousseau SM. Coagulation — cancer interaction in situ in renal cell carcinoma. Blood 1986; 68: 394-399
    PubMedGoogle Scholar
  • 39 Zacharski LR, Memoli VA, Rousseau SM, Kisiel W. Occurrence of blood coagulation factors in situ in small cell carcinoma of the lung. Cancer 1987; 60: 2675-2681
    CrossrefPubMedGoogle Scholar
  • 40 Ádány R, Belkin A, Vasilevskaya T, Muszbek L. Identification of blood coagulation factor XIII in human peritoneal macrophages. Eur J Cell Biol 1985; 38: 171-173
    PubMedGoogle Scholar
  • 41 Chapman HA, Allen LC, Stone OL, Fair DS. Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease. J Clin Invest 1985; 75: 2030-2037
    CrossrefPubMedGoogle Scholar
  • 42 Rothberger H, McGee MP. Generation of coagulation factor V activity by cultured rabbit alveolar macrophages. J Exp Med 1984; 160: 1880-1890
    CrossrefPubMedGoogle Scholar
  • 43 Osterud B, Lindahl U, Seljelid R. Macrophages produce blood coagulation factors. FEBS Lett 1980; 120: 41-43
    CrossrefPubMedGoogle Scholar
  • 44 Osterud B, Bogwald J, Lindahl U, Seljelid R. Production of blood coagulation factor V and tissue thromboplastin by macrophages in vitro. FEBS Lett 1981; 127: 154-156
    CrossrefPubMedGoogle Scholar
  • 45 Lindahl U, Kolset SO, Bogwald J, Osterud B, Seljelid R. Studies, with a luminogenic peptide substrate, on blood coagulation factor XI Xa produced by mouse peritoneal macrophages. Biochem J 1982; 206: 231-237
    CrossrefPubMedGoogle Scholar
  • 46 Van Dam-Mieras MC E, Muller AD, van Deijk WA, Hemker HC. Clotting factors secreted by monocytes and macrophages: analytical considerations. Thromb Res 1985; 37: 09-19
    CrossrefPubMedGoogle Scholar
  • 47 Shelley BW, Juhlin L. Induction of fibrin thrombi by monocytes. Nature 1977; 270: 343-344
    CrossrefPubMedGoogle Scholar
  • 48 Dvorak AM, Connell AB, Proppe K, Dvorak HF. Immunologic rejection of mammary adenocarcinoma (TA-3-St) in C57BL/6 mice: Participation of neutrophils and activated macrophages with fibrin formation. J Immunol 1978; 120: 1240-1248
    PubMedGoogle Scholar