Intratumoral Fibrin Stabilization

  • L. Muszbek
  • R. Ádány


Fibrin deposition in the interstitial space of the stroma of malignant tumours is a frequent finding (see reviews by Rickles and Edwards 1983; Dvorak et al. 1983) and can be regularly observed, among others, in lymph nodes with Hodgkin’s disease (Harris et al. 1982). Hypotheses based on supporting experimental and clinical data implicate intratumoral fibrin in the promotion of tumour growth and metastasis formation (Laki 1974; Dvorak et al. 1983). Fibrin may serve as a barrier making tumour cells relatively inaccessible for the host’s immune response, may play an important role in tumour angiogenesis and desmoplasia and might support the implantation of tumour cells at metastatic sites.


Factor Xiii Fibrin Deposit Fibrin Network Activate Factor Xiii Naphthyl Acetate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ádány R, Belkin A, Vasilevskaya T, Muszbek L (1985) Identification of blood coagulation factor XIII in human peritoneal mcrophages. Eur J Cell Biol 38:171–173PubMedGoogle Scholar
  2. Ádány R, Nemes Z, Muszbek L (1987a) Characterization of factor XIII containing-macrophages in lymph nodes with Hodgkin’s disease. Br. J Cancer 55:421–42PubMedCrossRefGoogle Scholar
  3. Ádány R, Kappelmayer J, Muszbek L (1987b) Expression of FXIII subunit a in different types of human macrophages. In: Mauri C, Rizzo SC, Ricevuti G (eds) The biology of phagocytes in health and disease, Pergamon, OxfordGoogle Scholar
  4. Ádàny R, Kiss A, Muszbek L (1987c) Factor XIII: a marker of mono-and megakariocytopoiesis. Br J Haematol 67:167–172PubMedCrossRefGoogle Scholar
  5. Ádány R, Glukhova MA, Kabakov AY, Muszbek L (1988) Characterization of human connective tissue cells containing factor XIII subunit a. J Clin Pathol, (in press)Google Scholar
  6. Aoki N, Harpel PC (1984) Inhibitors of the fibrinolytic enzyme system. Semin Thromb Hemost 10:24–41PubMedCrossRefGoogle Scholar
  7. Beck E, Duckert F, Ernst M (1961) The influence of fibrin stabilizing factor on the growth of fibroblasts in vitro and wound healing. Thromb Diath Haemorrh 6:485–491PubMedGoogle Scholar
  8. Bruhn HD (1981) Growth regulation of vessel wall cells and of tumor cells by thrombin, factor XIII and fibronectin. Thromb Haemost 46:762PubMedGoogle Scholar
  9. Bruhn HD, Pohl J (1981) Growth regulation of fibroblasts by thrombin, factor XIII and fibronectin. Klin Wochenschr 59:141–146CrossRefGoogle Scholar
  10. Bruhn HD, Zurborn KH (1983) Influences of clotting factors (thrombin, factor XIII) and of fibronectin on the growth of tumor cells and leukemic cells in vitro. Blut 46:85–88PubMedCrossRefGoogle Scholar
  11. Curatolo L, Colucci M, Cambini AL, Poggi A, Morasca L, Donati MB, Semeraro N (1979) Evidence that cells from experimental tumours can activate coagulant factor X. Br J Cancer 40:228–233PubMedCrossRefGoogle Scholar
  12. Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skirer L (1985) Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 44:139–266PubMedCrossRefGoogle Scholar
  13. Dimitriu-Bona A, Burmester GR, Waters SJ, Winchester RJ (1983) Human mononuclear phagocyte differentiation antigens. I. Patterns of antigenic expression on the surface of human monocytes and mcrophages defined by monoclonal antibodies. J Immunol 130:145–152PubMedGoogle Scholar
  14. Duffy MJ, O’Grady PO (1984) Plasminogen activator and cancer. Eur J Cancer Clin Oncol 20:577–582PubMedCrossRefGoogle Scholar
  15. Dvorak AM, Connell AB, Proppe K, Dvorak HF (1978) Immunologic rejection of mammary adenocarcinoma (TA3-St) in C57BL/6 mice: participation of neutrophils and activated macrophages with fibrin formation. J Immunol 120:1240–1248PubMedGoogle Scholar
  16. Dvorak HF, Senger DR, Dvorak AM (1983) Fibrin as a component of the tumor stroma: origins and biological significance. Cancer Metastasis Rev 2:41–73PubMedCrossRefGoogle Scholar
  17. Dvorak HF, Harvey S, McDonagh J (1984) Quantitation of fibrinogen influx and fibrin deposition and turnover in line 1 and line 10 quinea pig carcinomas. Cancer Res 44:3348–3354PubMedGoogle Scholar
  18. Edwards RL, Rickles FR, Cronlund M (1981) Abnormalities of blood coagulation in patients with cancer: mononuclear cell tissue factor generation. J Lab Clin Med 98:917–928PubMedGoogle Scholar
  19. Gordon ST (1981) A proteolytic procoagulant associated with malignant transformation. J Histochem Cytochem 29:457–463PubMedCrossRefGoogle Scholar
  20. Gordon ST, Franks JJ, Lewis B (1975) Cancer procoagulant A: a factor X activating procoagulant from malignant tissue. Thromb Res 6:127–137PubMedCrossRefGoogle Scholar
  21. Guarini A, Acero R, Alessio G, Donati MB, Semeraro N, Mantovani A (1984) Procoagulant activity of macrophages associated with different murine neoplasms. Int J Cancer 34:581–586PubMedCrossRefGoogle Scholar
  22. Harris NL, Dvorak AM, Smith J, Dvorak HF (1982) Fibrin deposits in Hodgkin’s disease. Am J Pathol 108:119–129PubMedGoogle Scholar
  23. Henriksson P, Becker S, Lynch G, McDonagh J (1985) Identification of factor XIII in human monocytes and macrophages. J Clin Invest 76:528–534PubMedCrossRefGoogle Scholar
  24. Israels ED, Paraskevas F, Israels LG (1973) Immunological studies of coagulation factor XIII. J Clin Invest 52:2398–2403PubMedCrossRefGoogle Scholar
  25. Jansen JWCM, Haverkate F, Koopman J, Nieuwenhuis HK, Kluft C, Boschman TAC (1987) Influence of Factor XIIIa activity on human whole blood clot lysis in vitro. Thromb Haemost 57:171–175PubMedGoogle Scholar
  26. Kasai S, Kunimoto T, Nitta K (1983) Cross-linking of fibrin by activated factor XIII stimulates attachment, morphological changes and proliferation of fibroblasts. Biomed Res 4:155–160Google Scholar
  27. Key M (1983) Macrophages in cancer metastases and their relevance to metastatic growth. Cancer Metastasis Rev 2:75–88PubMedCrossRefGoogle Scholar
  28. Kradin RL, Lynch GW, Kurnick JT, Erikson M, Colvin RB, McDonagh J (1987) Factor XIII is synthetized and expressed on the surface of U937 cells and alveolar macrophages. Blood 69:778–785PubMedGoogle Scholar
  29. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRefGoogle Scholar
  30. Laki K (1974) Fibrinogen and metastases. J Med 5:32–37PubMedGoogle Scholar
  31. Layer GT, Burnand KG, Gaffney PJ, Cederholm-Williams SA, Mahmoud M, Houlbrook S, Pattison M (1987) Tissue Plasminogen activators in breast cancer. Thromb Res 45:601–607PubMedCrossRefGoogle Scholar
  32. Lorand L, Dickenman RC (1955) Assay method for the “fibrin-stabilizing factor”. Proc Soc Exp Biol 89:45–48PubMedGoogle Scholar
  33. Lorenzet R, Peri G, Locati D, Allavena P, Colucci M, Semeraro N, Mantovani A, Donati MB (1983) Generation of procoagulant activity by mononuclear phagocytes: A possible mechanism contributing to blood clotting activation within malignant tissues. Blood 62:271–273PubMedGoogle Scholar
  34. Muszbek L, Laki K (1984) Interaction of thrombin with proteins other than fibrinogen (thrombin susceptible bonds). Activation of FXIII. In: Machovich R (ed) The thrombin. CRC, Boca Raton, pp 321–342Google Scholar
  35. Muszbek L, Ádány R, Szegedi G, Polgár J, Kávai M (1985) Factor XIII of blood coagulation in human monocytes. Thromb Res 37:401–410PubMedCrossRefGoogle Scholar
  36. Nicolson GN (1982) Cancer metastasis: Organ colonization and the cell surface properties of malignant cells. Biochim Biophys Acta 695:113–176PubMedGoogle Scholar
  37. Rickles FR, Edwards RL (1983) Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 62:14–31PubMedGoogle Scholar
  38. Sakata Y, Aoki N (1980) Cross-linking of α2-plasmin inhibitor to fibrin by fibrin-stabilizing factor. J Clin Invest 65:290–297PubMedCrossRefGoogle Scholar
  39. Sakata Y, Aoki N (1982) Significance of cross-linking of α2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis. J Clin Invest 69:536–542PubMedCrossRefGoogle Scholar
  40. Ueyama M, Urayama T (1977) The role of factor XIII in fibroblast proliferation. Jpn J Exp Med 48:135–142Google Scholar
  41. VanDeWater L, Tracy PB, Aronson D, Mann KG, Dvorak HF (1985) Tumor cell generation of thrombin via prothrombinase assembly. Cancer Res 45:5521–5525Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • L. Muszbek
    • 1
  • R. Ádány
    • 1
  1. 1.Department of Clinical ChemistryUniversity School of MedicineDebrecenHungary

Personalised recommendations