1887

Abstract

SUMMARY

Previous studies in this laboratory have quantified the fibrinolytic activity of herpesvirus-transformed cell lines and implicated the proteolytic capacity of cloned cell lines in the formation of primary and metastatic tumours. Because of the involvement of proteases in tumourigenesis in this system, we examined the effect of various protease inhibitors (α-1-antitrypsin, leupeptin and α-2-macroglobulin), as well as hamster serum containing acute phase proteins generated in response to physiological trauma, on the fibrinolytic capacity of a herpes simplex virus type 2-transformed hamster cell line. The effects of the various inhibitors on cell growth, fibrinolysis and tumourigenesis were examined. Leupeptin, α-1-antitrypsin, α-2-macroglobulin and hamster serum containing acute phase proteins were capable of inhibiting fibrinolysis , were not toxic to the cells and their action was reversible, while injection of a mixture of protease inhibitor and transformed cells resulted in delayed tumour development.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-60-1-15
1982-05-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/60/1/JV0600010015.html?itemId=/content/journal/jgv/10.1099/0022-1317-60-1-15&mimeType=html&fmt=ahah

References

  1. Adelman S. F., Howett M. K., Rapp F. 1980; Quantification of plasminogen activator associated with herpesvirus-transformed cells. Journal of General Virology 50:101–110
    [Google Scholar]
  2. Adelman S. F., Howett M. K., Rapp F. 1981; Tumorigenicity of herpesvirus-transformed cells correlates with production of plasminogen activator. Molecular and Cellular Biology 1:408–417
    [Google Scholar]
  3. Aoyagi T., Umezawa H. 1975; Structures and activities of protease inhibitors of microbial origin. In Proteases and Biological Control vol 2: pp 429–451 Edited by Reich E., Rifkin D., Shaw E. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  4. Barrett A. J., Starkey P. M. 1974; The unique nature of the interaction of a2-macroglobulin with proteinases. In Proteinase Inhibitors pp 14–22 Edited by Fritz H., Tschesche H., Green L. J., Truscheit E. Berlin: Springer-Verlag;
    [Google Scholar]
  5. Baugh R. J., Schnebli H. P. 1980; Role and potential therapeutic value of proteinase inhibitors in tissue destruction. In Proteinases and Tumor Invasion vol 6: pp 157–180 Edited by Strauli P., Barrett A. J., Baici A. Monograph Series of the European Organization for Research on Treatment of Cancer New York: Raven Press;
    [Google Scholar]
  6. Collen D. 1980; Inhibitors of fibrinolysis. In Fibrinolysis pp 130–144 Edited by Kline D. L., Reddy K. N. N. New York: CRC Press;
    [Google Scholar]
  7. Collen D., Billiau A., Edy J., Desomer P. 1977; Identification of the human plasma proteins which inhibit fibrinolysis associated with malignant cells. Biochimica et Biophysica Acta 499:194–201
    [Google Scholar]
  8. Duff R., Rapp F. 1971; Oncogenic transformation of hamster cells after exposure to herpes simplex virus type 2. Nature New Biology 233:48–50
    [Google Scholar]
  9. Frommer W., Junge B., Muller L., Schmidt D., Truscheit E. 1979; New enzyme inhibitors from microorganisms. Planta Medico 35:195–217
    [Google Scholar]
  10. Goetz I. E., Weinstein C., Roberts E. 1972; Effects of protease inhibitors on growth of hamster tumor cells in culture. Cancer Research 32:2469–2474
    [Google Scholar]
  11. Harpel P. C. 1976; Human a2-macroglobulin. Methods in Enzymology 45:639–645
    [Google Scholar]
  12. Harpel P. C., Mosesson M. W., Cooper N. R. 1975; Studies on the structure and function of a2-macroglobulin and Cl inactivator. In Proteases and Biological Control vol 2: pp 387–404 Edited by Reich E., Rifkin D., Shaw E. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  13. Harvey H. A., Lipton A., Albright C., Katz M., Troll W., Rapp F. 1977; Lack of inhibition of metastases by proteolytic inhibitors in an experimental herpesvirus system. Proceedings of the American Association for Cancer Research 18:68
    [Google Scholar]
  14. Heimburger N. 1975; Proteinase inhibitors of human plasma – their properties and control functions. In Proteases and Biological Control vol 2: pp 367–386 Edited by Reich E., Rifkin D., Shaw E. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  15. Howett M. K., High C. S., Rapp F. 1978; Production of plasminogen activator by cells transformed by herpesviruses. Cancer Research 38:1075–1078
    [Google Scholar]
  16. Hozumi M., Igawa M., Sugemura T., Takeuchi T., Umezawa H. 1972; Inhibition of tumorigenesis in mouse skin by leupeptin, a protease inhibitor from Actinomycetes. Cancer Research 32:1725–1728
    [Google Scholar]
  17. Jeppsson J. O., Laurell C. B. 1975; Function and chemical composition of a, antitrypsin. In Proteases and Biological Control vol 2: pp 405–414 Edited by Reich E., Rifkin D., Shaw E. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  18. Jordan H. 1976; The α-macroglobulins of rat serum. Journal of Biochemistry 159:643–650
    [Google Scholar]
  19. Kakizoe T., Esumi H., Kawachi T., Sugemura T., Takeuchi T., Umezawa H. 1977; Further studies on the effect of leupeptin, a protease inhibitor, on induction of bladder tumors in rats by N-butyl-N– (4-hydroxybutyl) nitrosamine. Journal of the National Cancer Institute 59:1503–1508
    [Google Scholar]
  20. Kline D. L., Reddy K. N. N. (editors) 1980 Fibrinolysis New York: CRC Press;
    [Google Scholar]
  21. Kress L. F., Laskowski M. sr 1974; Purification, properties and composition of α1-trypsin inhibitor from human plasma. In Proteinase Inhibitors pp 23–30 Edited by Fritz H., Tschesche H., Greene L. J., Truscheit E. Berlin: Springer-Verlag;
    [Google Scholar]
  22. Lage A., Diaz J. W., Gonzalez I. 1978; Effect of proteinase inhibitors in experimental tumors. Neoplasma 25:257–259
    [Google Scholar]
  23. Ossowski L., Quigley J. P., Reich E. 1975; Plasminogen, a necessary factor for cell migration in vitro. In Proteases and Biological Control vol 2: pp 901–913 Edited by Reich E., Rifkin D., Shaw E. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  24. Reich E., Rifkin D., Shaw E. (editors) 1975 Proteases and Biological Control vol 2: New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  25. Saito M., Hagiwara T., Aoyagi T., Nagai Y. 1972; Leupeptin, a protease inhibitor, inhibits the PHA-stimulated DNA synthesis in guinea pig blood lymphocytes. Japanese Journal of Experimental Medicine 42:509–511
    [Google Scholar]
  26. Saito M., Yoshizawa T., Aoyagi T., Nagai Y. 1973; Involvement of proteolytic activity in early events in lymphocyte transformation by phytohemagglutinin. Biochemical and Biophvsical Research Communications 52:569–575
    [Google Scholar]
  27. Starkey P. M., Barrett A. J. 1977; α2-Macroglobulin, a physiological regulator of proteinase activity. In Proteinoses in Mammalian Cells and Tissues pp 663–696 Edited by Barrett A. J. Amsterdam: Elsevier/North-Holland;
    [Google Scholar]
  28. Sträuli P., Barrett A. J., Baici A. (editors) 1980 Proteinoses and Tumor Invasion vol 6: Monograph Series of the European Organization for Research on Treatment of Cancer New York: Raven Press;
    [Google Scholar]
  29. Travis J., Johnson D., Pannell R. 1974; Properties of human α1antitrypsin. In Proteinase Inhibitors pp 31–39 Edited by Fritz H., Tschesche H., Greene L. J., Truscheit E. Berlin: Springer-Verlag;
    [Google Scholar]
  30. Troll W., Klassen A., Janoff A. 1970; Tumorigenesis in mouse skin: inhibition by synthetic inhibitors of proteases. Science 169:1211–1213
    [Google Scholar]
  31. Troll W., Meyn M. S., Rossmann T. G. 1978; Mechanisms of protease action in carcinogenesis. In Carcinogenesis vol 2: pp 301–312 Edited by Slaga T. J., Sivak A., Boutwell R. K. New York: Raven Press;
    [Google Scholar]
  32. Umezawa H. 1976; Structures and activities of protease inhibitors of microbial origin. Methods in Enzymology 45:678–695
    [Google Scholar]
  33. Umezawa H. 1977; Protease inhibitors produced by microorganisms. Acta Biologica et Medico Germanica 36:1899–1915
    [Google Scholar]
  34. Umezawa H. 1978; Metabolites under preclinical development for cancer treatment. Recent Results in Cancer Research 63:120–134
    [Google Scholar]
  35. Umezawa H., Aoyagi F. 1977; Activities of proteinase inhibitors of microbial origin. In Proteinases in Mammalian Cells and Tissues pp 637–662 Edited by Barrett A. J. Amsterdam: Elsevier/North-Holland;
    [Google Scholar]
  36. Unkeless J. C., Tobia A., Ossowski L., Quigley J. P., Rifkin D. B., Reich E. 1973; An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. I. Chick embryo fibroblast cultures transformed by avian RNA tumor viruses. Journal of Experimental Medicine 137:85–111
    [Google Scholar]
  37. Wingender W. 1974; Proteinase inhibitors of microbial origin – a review. In Proteinase Inhibitors pp 548–559 Edited by Fritz H., Tschesche H., Greene L. J., Truscheit E. Berlin: Springer-Verlag;
    [Google Scholar]
  38. Yamanishi K., Rapp F. 1979; Production of plasminogen activator by human and hamster cells infected with human cytomegalovirus. Journal of Virology 31:415–419
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-60-1-15
Loading
/content/journal/jgv/10.1099/0022-1317-60-1-15
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error