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Blood and tissue fibrinolytic profiles in patients with colorectal carcinoma

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International Journal of Clinical and Laboratory Research

Summary

In patients with colorectal cancer, profound alterations of the plasminogen activator system have been described at the tumor level, but conflicting results have been obtained for fibrinolytic parameters in plasma. Components of the fibrinolytic system, including tissue-type and urokinase-type plasminogen activators and their inhibitors type 1 and 2, were measured in tissue and/or plasma from 41 patients with colorectal cancer and in 40 controls. Procoagulant activity of freshly isolated mononuclear cells (basal activity) and the procoagulant activity and fibrinolytic proteins produced by the cells after incubation for 18 h without exogenous stimulation were also evaluated. Malignant tissue extracts had significantly higher levels of urokinase-type plasminogen activator and plasminogen activator inhibitor-1, but lower levels of tissue-type plasminogen activator than normal mucosa. Plasminogen activator inhibitor-1 alone was higher in advanced (Dukes' stages C+D) than limited (B) tumors. Plasminogen activator inhibitor-2 was not different in malignant tissue and normal mucosa. Plasma levels of plasminogen activator inhibitor-1 antigen were significantly increased in cancer patients compared with controls, but there were no differences in tissue-type and urokinase-type plasminogen activator, in plasminogen activator inhibitor-2, and D-dimer levels. Intra-patient analysis revealed no significant correlation between tumor and plasma levels of plasminogen activators or type 1 inhibitor. Tissue-type plasminogen activator, but not the urokinase type or inhibitor type 1, was higher in venous than in arterial blood collected at the tumor site during surgery. Basal procoagulant activity of mononuclear cells and the procoagulant activity and inhibitor type-2 produced by the cells after shortterm culture were comparable in patients and controls. These findings indicate that, at least in our patients with colorectal cancer, the profound changes occurring at tumor level are barely detectable in the blood. Thus, the clinical relevance of plasma fibrinolytic parameters, especially urokinase-type plasminogen activator antigen, as tumor markers in colorectal cancer remains to be established.

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References

  1. Graeff H, Harbeck N, Pache L, Wilhelm O, Janicke F, Schmitt M. Prognostic impact and clinical relevance of tumor-associated proteases in breast cancer. Fibrinolysis 1992; 6 [Suppl 4]: 45.

    Google Scholar 

  2. Duffy MJ. Urokinase-type plasminogen activator and malignancy. Fibrinolysis 1993; 7: 295.

    Article  CAS  Google Scholar 

  3. Grondahl-Hansen J, Christensen IJ, Rosenquist C, Brunner N, Mouridsen HT, Dano K, Blichert-Toft M. High levels of urokinase-type plasminogen activator and its inhibitor PAI-l in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Res 1993; 53:2513.

    PubMed  CAS  Google Scholar 

  4. Mulcahy HF, Duffy MJ, Gibbons D, McCarthy P, Parfray NA, O'Donoghue UP, Sheahan K. Urokinase-type plasminogen activator and outcome in Dukes' B colorectal cancer. Lancet 1994: 344:583.

    Article  PubMed  CAS  Google Scholar 

  5. Ganesh S, Sier CFM, Griffioen G, Vloedgraven HJM, Boer A de, Welvaart K, Velde CJH van de; Krieken JHJM van; Verheijen JH, Lamers CBHW, Verspaget HW. Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer. Cancer Res 1994; 54: 4065.

    PubMed  CAS  Google Scholar 

  6. Fazioli F, Blasi F. Urokinase-type plasminogen activator and its receptor: new targets for anti-metastatic therapy? Trends Pharmacol Sci 1994; 15: 25

    Article  PubMed  CAS  Google Scholar 

  7. Ganesh S, Sier CFM, Heerding MM, Griffioen G, Lamers CBHW, Verspaget HW. Urokinase receptor and colorectal cancer survival. Lancet 1994; 344: 401.

    Article  PubMed  CAS  Google Scholar 

  8. Fukao H, Tanaka N, Ueshima S, Okada K, Yasutomi M, Matsuo O. Plasminogen activator inhibitor in stomach and colorectal carcinomas. Semin Thromb Hemost 1991; 17: 276.

    Article  PubMed  CAS  Google Scholar 

  9. Sier CFM, Verspaget HW, Griffioen G, Verheijen JH, Quax PHA, Dooijewaard G, Bruin PAF de, Lamers CBHW. Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Gastroenterology 1991; 101: 1522.

    PubMed  CAS  Google Scholar 

  10. Sumiyoshi K, Serizawa K, Urano T, Takada Y, Takada A, Bada S. Plasminogen activator system in human breast cancer. Int J Cancer 1992; 50: 345.

    Article  PubMed  CAS  Google Scholar 

  11. Bouchet C, Spyratos F, Martin PM, Hacene K, Gentile A, Oglobine J. Prognostic value of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-I and PAI-2 in breast carcinomas. Br J Cancer 1994; 69: 398.

    PubMed  CAS  Google Scholar 

  12. Nakamura M, Konno H, Tanaka T, Maruo Y, Nishino N, Aoki K, Baba S, Sakaguchi S, Takada Y, Takada A. Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues. Thromb Res 1992; 65: 709.

    Article  PubMed  CAS  Google Scholar 

  13. Gleeson NC, Gonsalves R, Bonnar J. Plasminogen activator inhibitors in endometrial adenocarcinoma. Cancer 1993; 72: 1670.

    Article  PubMed  CAS  Google Scholar 

  14. Kirchheimer JC, Huber K, Wagner O, Binder BR. Pattern of fibrinolytic parameters in patients with gastrointestinal carcinomas. Br J Haematol 1987; 66: 85.

    PubMed  CAS  Google Scholar 

  15. Nishino N, Aoki K, Tokura Y, Sakaguchi S, Takada Y, Takada A. The urokinase type plasminogen activator in cancer of digestive tracts. Thromb Res 1988; 50: 527.

    Article  PubMed  CAS  Google Scholar 

  16. Mellbring G. Fibrinolysis and malignancy. In: Nilsson TK, Boman K, Jansson JH, eds. Clinical aspects of fibrinolysis. Stockholm: Almqvist and Wiksell; 1991: 141–157.

    Google Scholar 

  17. Duijnhoven EM van; Lustermans FAT, Wersch JWJ van. Evaluation of the coagulation/fibrinolysis balance in patients with colorectal cancer. Haemostasis 1993; 23: 168.

    PubMed  Google Scholar 

  18. Huber K, Kirchheimer JC, Sedlmayer A, Bell C, Ermler D, Binder BR. Clinical value of determination of urokinsae-type plasminogen activator antigen in plasma for detection of colorectal cancer: comparison with circulating tumor-associated antigens CA 19-9 and carcinoembryonic antigen. Cancer Res 1993; 53: 1788.

    PubMed  CAS  Google Scholar 

  19. Morgan D, Edwards RL, Rickels FR. Monocyte procoagulant activity as a peripheral marker of clotting activation in cancer patients. Haemostasis 1988; 18: 55

    PubMed  CAS  Google Scholar 

  20. Semeraro N, Montemurro P, Conese M, Giordano D, Stella M, Restaino A, Cagnazzo G, Colucci M. Procoagulant activity of mononuclear phagocytes from different anatomical sites in patients with gynecological malignancies. Int J Cancer 1990; 45: 251.

    Article  PubMed  CAS  Google Scholar 

  21. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72:248.

    Article  PubMed  CAS  Google Scholar 

  22. Kluft C, Verheijen JH. Leiden fibrinolysis working party: blood collection and handling procedures for assessment of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). Fibrinolysis 1990; 4 [Suppl 2]: 155.

    Article  CAS  Google Scholar 

  23. Semeraro N, Biondi A, Lorenzet R, Locati D, Mantovani A, Donati MB. Direct induction of tissue factor synthesis by endotoxin in human macrophages from diverse anatomical sites. Immunology 1983; 50: 529.

    PubMed  CAS  Google Scholar 

  24. Colucci M, Paramo JA, Collen D. Generation in plasma of a fast acting inhibitor of plasminogen activator in response to endotoxin. J Clin Invest 1985; 75: 818.

    Article  PubMed  CAS  Google Scholar 

  25. Gelister JSK, Jass JR, Mahmoud M, Lewin MR, Gaffney PJ, Boulos PB. Role of urokinase in colorectal neoplasia. Br J Surg 1987; 74: 460.

    Article  PubMed  CAS  Google Scholar 

  26. Sim P-S, Stephens RW, Fayle DRH, Doe WF. Urokinase-type plasminogen activator in colorectal carcinomas and adenomatous polyps: quantitative expression of active and proenzyme. Int J Cancer 1988; 42: 483.

    Article  PubMed  CAS  Google Scholar 

  27. Pujade-Lauraine E, Lu H, Mirshahi S, Soria J, Soria C, Bernadou A, Kruithof EKO, Lijnen HR, Burtin P. The plasminogen-activation system in ovarian tumors. Int J Cancer 1993; 55: 27.

    Article  PubMed  CAS  Google Scholar 

  28. Kirchheimer JC, Kohl H, Tatra G, Binder BR. Relationship between plasma levels of components of the fibrinolytic system and acute-phase reactants in patients with uterine malignancies. Eur J Clin Invest 1990; 20: 79.

    PubMed  CAS  Google Scholar 

  29. Grondahl-Hansen J, Agerlin N, Munkholm-Larsen P, Bach F, Nielsen LS, Dombernowsky P, Dano K. Sensitive and specific enzyme-linked immunosorbent assay for urokinase-type plasminogen activator and its application to plasma from patients with breast cancer. J Lab Clin Med 1988; 111: 42.

    PubMed  CAS  Google Scholar 

  30. Saito K, Nagashima M, Iwata M, Hamada H, Sumiyoshi K, Takada Y, Takada A. The concentration of tissue plasminogen activator and urokinase in plasma and tissues of patients with ovarian and uterine tumors. Thromb Res 1990; 58: 355.

    Article  PubMed  CAS  Google Scholar 

  31. Declerck PJ, Moreau H, Jespersen J, Gram J, Kluft C. Multicenter evaluation of commercially available methods for the immunological determination of plasminogen activator inhibitor-1 (PAI-1). Thromb Haemost 1993; 70: 858.

    PubMed  CAS  Google Scholar 

  32. Gram J, Declerck PJ, Sidelmann J, Jespersen J, Kluft C, Multicentre evaluation of commercial kit methods: plasminogen activator inhibitor activity. Thromb Haemost 1993; 70: 852.

    PubMed  CAS  Google Scholar 

  33. Casslen B, Astedt B. The plasminogen activating system in ovarian carcinomas. Fibrinolysis 1992; 6 [Suppl 4]: 65.

    Google Scholar 

  34. 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.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Patologia Generale, Università di Bari, Policlinico, Piazza G. Cesare 11, 1-70124, Bari, Italy

    P. Montemurro, M. Conese, M. Colucci & N. Semeraro

  2. Istituto di Clinica Chirurgica, Università di Bari, Bari, Italy

    D. F. Altomare & V. Memeo

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  1. P. Montemurro
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  2. M. Conese
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  3. D. F. Altomare
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  4. V. Memeo
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  5. M. Colucci
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  6. N. Semeraro
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Montemurro, P., Conese, M., Altomare, D.F. et al. Blood and tissue fibrinolytic profiles in patients with colorectal carcinoma. Int J Clin Lab Res 25, 195–200 (1995). https://doi.org/10.1007/BF02592697

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  • DOI: https://doi.org/10.1007/BF02592697

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