Skip to main content
SpringerLink
Log in

Proteolytic and metastatic activities of clones derived from a methylcholanthrene-induced murine fibrosarcoma

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Eighteen clones of a methylcholanthrene-induced murine fibrosarcoma (3AM) which were heterogeneous with respect to metastatic potentials and in vivo growth rates were examined for five different protease activities: acid protease (cathepsin D), BANA hydrolase (cathepsin B), neutral protease, collagenase, and plasminogen activator. Homogenates of the solid tumors produced by the clones were heterogeneous with respect to the activities of the proteases; these activities were in all cases (except plasminogen activator) higher than those obtained for normal muscle tissue. There was, however, no correlation between any of these protease activities and the metastatic potential or in vivo growth rates. The cathepsin B activity has also been evaluated on the cultured cells of the various clones. Results similar to that of the in vivo study were obtained. Analysis of the enzyme activity of the cell culture and of organ culture media, however, revealed no cathepsin B activity. It is concluded that the measurement of any one biochemical parameter such as proteolysis may not be sufficient to establish a correlation with the overall process of metastasis; a more precise dissection of the individual steps culminating in metastasis may provide a more fruitful approach to this problem.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barrett, A. J., 1972, A new assay for cathepsin B and other thiol proteinases. Analytical Biochemistry, 47, 280–293.

    Google Scholar 

  2. Brunson, K. W., Beattie, G., and Nicolson, G. L., 1978, Selection and altered properties of brain-colonizing metastatic melanoma. Nature, London, 270, 543–545.

    Google Scholar 

  3. Charney, J., and Tomarelli, R., 1947, A colorimetric method for the determination of the proteolytic activity of duodenal juice. Journal of Biological Chemistry, 171, 501–515.

    Google Scholar 

  4. Chibber, B. A., Niles, R. M., Prehn, L., and Sorof, S., 1975, High extracellular fibrinolytic activity of tumors and control normal tissues. Biochemical and Biophysical Research Communications, 65, 806–812.

    Google Scholar 

  5. Dabbous, M. K., Roberts, A. N., and Brinkley, S. B., 1977, Collagenase and neutral protease activities in cultures of rabbit VX-2 carcinoma. Cancer Research, 37, 3537–3542.

    Google Scholar 

  6. Dexter, D. L., Kowalski, H. M., Blazar, B. A., Fligiel, Z., Vogel, R., and Heppner, G. H., 1978, Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Research, 38, 3174–3181.

    Google Scholar 

  7. Fidler, I. J., 1978, Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer Research, 38, 2651–2660.

    Google Scholar 

  8. Fidler, I. J., and Hart, I. R., 1981, The origin of metastatic heterogeneity in tumors. European Journal of Cancer, 17, 487–494.

    Google Scholar 

  9. Fidler, I. J., and Kripke, M. L., 1977, Metastasis results from preexisting variant cells within a malignant tumor. Science, New York, 197, 893–895.

    Google Scholar 

  10. Harpel, P. C., 1976, Human α2-macroglobulin. Methods in Enzymology, 35, 639–652.

    Google Scholar 

  11. Harris, E. D., Faulker, C. S., and Wood, S., 1972, Collagenase in carcinoma cells. Biochemical and Biophysical Research Communications, 48, 1247–1253.

    Google Scholar 

  12. Hartree, E. F., 1972, Determination of protein: A modification of the Lowry-method that gives a linear photometric response. Analytical Biochemistry, 48, 422–427.

    Google Scholar 

  13. Hashimoto, K., Yamanishi, Y., Maeyens, E., Dabbous, M. K., and Kanzaki, T., 1973, Collagenolytic activities of squamous cell carcinoma of the skin, Cancer Research, 33, 2790–2801.

    Google Scholar 

  14. Jones, P. A., Laug, W. E., and Benedict, W. F., 1975, Fibrinolytic activity in a human fibrosarcoma cell line and evidence for the induction of plasminogen activator secretion during tumor formation. Cell, 6, 245–252.

    Google Scholar 

  15. Jones, P. A., Rhim, J. S., Isaacs, H. J., and McAllister, R. M., 1975, The relationship between tumorigenicity, growth in agar, and fibrinolytic activity in a line of human osteosarcoma cells. International Journal of Cancer, 16, 616–621.

    Google Scholar 

  16. Kirsche, H., Langer, J., Riemann, S., Wideranders, B., Ansorge, B., and Bradley, P., 1980, Lysosomal cysteine proteinases. Protein Degradation in Health and Disease, Ciba Foundation Symposium, 75, 15–35.

    Google Scholar 

  17. Kripke, M. L., Gruys, E., and Fidler, I. J., 1978, Metastatic heterogeneity of cells from an ultraviolet-light-induced murine fibrosarcoma of recent origin. Cancer Research, 38, 2962–2967.

    Google Scholar 

  18. Labrosse, K. R., and Liener, I. E., 1978, Collagenolytic activities in methylcholanthrene-induced fibrosarcomas in mice. Molecular and Cellular Biochemistry, 19, 181–191.

    Google Scholar 

  19. Liotta, L. A., Abe, S., Robey, P. G., and Martin, G. R., 1979, Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proceedings of the National Academy of Sciences, USA, 76, 2268–2272.

    Google Scholar 

  20. Liotta, L. A., Tryggvason, K., Barbisa, S., Hart, I., Foltz, C. M., and Shafie, E., 1980, Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature, London, 284, 67–68.

    Google Scholar 

  21. Markus, G., Camiolo, S. M., Evers, J. L., Corasanti, J. G., and Hobika, G. H., 1980, Plasminogen activators in human tumors. Developmental Biochemistry, 8, 577–602.

    Google Scholar 

  22. Masui, Y., Takemoto, T., Sakakibara, S., Hori, H., and Nagai, Y., 1977, Synthetic substrates for vertebrate collagenase. Biochemical Medicine, 17, 215–221.

    Google Scholar 

  23. McDonald, J. K., and Ellis, S., 1975, On the substrate specificity of cathepsin B1 and B2 including a new fluorogenic substrate for cathepsin B1. Life Sciences, 7, 1269–1276.

    Google Scholar 

  24. Mort, J. S., Recklies, A. D., and Poole, A. R., 1980, Characterization of a thiol protemase secreted by malignant human breast tumors. Biochimica et Biophysica Acta, 614, 134–143.

    Google Scholar 

  25. Nagase, H., Jackson, R. C., Brinckerhoff, C. E., Vatter, C. H., and Harris, E. D. Jscr., 1981, A precursor form of collagenase produced in cell-free system with mRNA from rabbit synovial cells. Journal of Biological Chemistry, 256, 11951–11954.

    Google Scholar 

  26. Nagy, B., Ban, J., and Brdar, B., 1977, Fibrinolysis associated with human neoplasis: production of plasminogen activator by human tumors. International Journal of Cancer, 19, 614–620.

    Google Scholar 

  27. Nicolson, G. L., Brunson, K. W., and Fidler, I. J., 1978, Specificity of arrest, survival, and growth of selected metastatic variant cell lines. Cancer Research, 38, 4105–4111.

    Google Scholar 

  28. Nielands, J. B., 1955, Lactic dehydrogenase of heart muscle. Methods in Enzymology, 1, 449–454.

    Google Scholar 

  29. Pietras, R. J., and Roberts, J. A., 1981, Cathepsin B-like enzymes. Subcellular distribution and properties in neoplastic and control cells from human ectocervis. Journal of Biological Chemistry, 256, 8536–8544.

    Google Scholar 

  30. Poole, A. R., Tiltman, K. J., Recklies, A. D., and Stoker, T. A. M., 1978, Differences in secretion of the proteinase cathepsin B at the edge of human breast carcinomas and fibroadenomas. Nature, London, 273, 545–547.

    Google Scholar 

  31. Poste, G., and Fidler, I. J., 1980, The pathogenesis of cancer metastasis. Nature, London, 283, 139–146.

    Google Scholar 

  32. Quigley, J. P., 1979, Proteolytic enzymes of normal and malignant cells. Surfaces of Normal and Malignant Cells, edited by R. O. Hynes (Chichester: John Wiley and Sons), pp. 247–285.

    Google Scholar 

  33. Recklies, A. D., Tiltman, K. J., Stocker, T. A. M., and Poole, A. R., 1980, Secretion of proteinase from the malignant and nonmalignant human breast tissue. Cancer Research, 40, 550–556.

    Google Scholar 

  34. Reich, E., 1974, Tumor-associated fibrinolysis. Control of Proliferation in Animal Cells, Cold Spring Harbor Conferences on Cell Proliferation, 1, 351–355.

    Google Scholar 

  35. San, R. H. C., Rice, J. M., and Williams, G. M., 1977, Lack of correlation between plasminogen activating factor production and tumorigenicity in rat liver epithelial cells. Cancer Letters, 3, 243–246.

    Google Scholar 

  36. Sasaki, M., Minakata, K., Yamamoto, H., Nieva, M., Kato, T., and Ito, N., 1977, A new serum component which specifically inhibits thiol proteinases. Biochemical and Biophysical Research Communications, 76, 917–924.

    Google Scholar 

  37. Sloane, B. F., and Dunn, J. R., 1981, Lysosomal cathepsin B: Correlation with metastatic potential. Science, New York, 212, 1151–1153.

    Google Scholar 

  38. Sloane, B. F., Honn, K. V., Sadler, J. G., Turner, W. A., Kimpson, J. J., and Taylor, J. D., 1982, Cathepsin B activity in B16 melanoma cells: a possible marker for metastatic potential. Cancer Research, 42, 980–986.

    Google Scholar 

  39. Snedecor, G. W., and Cochran, W. G., 1978, Statistical Methods, 6th ed. (Ames, Iowa: Iowa State University Press).

    Google Scholar 

  40. Starkey, P. M., and Barrett, A. J., 1973, Human cathepsin B1. Inhibition by α2-macroglobulin and other serum proteins. Biochemical Journal, 131, 823–831.

    Google Scholar 

  41. Steven, F. S., Podrazky, V., and Itzhaki, S., 1977, Evidence for the presence of a trypsin inhibitor within rabbit and mouse tumor cells. Biochimica et Biophysica Acta, 483, 211–214.

    Google Scholar 

  42. Strauli, P., Barrett, A. J., and Baici, A., 1980, Proteinases and tumor invasion (New York: Raven Press).

    Google Scholar 

  43. Sylven, B., and Bois-Svensson, I., 1965, On the chemical pathology of interstitial fluid: I. Proteolytic activities in transplanted mouse tumors. Cancer Research, 25, 458–468.

    Google Scholar 

  44. [44]Sylven, B., Snellman, O., and Strauli, P., 1974, Immunofluorescent studies on the occurrence of cathepsin B at tumor cell surfaces. Virchows Archiv B, Cell Pathology, 17, 97–112.

    Google Scholar 

  45. Talmadge, J. E., Starkey, J. R., and Stanford, D. R., 1981, In vitro characteristics of metastatic variant subclones of restricted genetic origin. Journal of Supramolecular Structure and Cellular Biochemistry, 15, 139–151.

    Google Scholar 

  46. Wang, B. S., McLoughlin, G. A., Richie, J. P., Mannick, J. A., 1980, Correlation of the production of plasminogen activator with tumor metastasis in B16 mouse melanoma cell lines. Cancer Research, 40, 280–292.

    Google Scholar 

  47. Wang, N., Liener, I. E., Hebbel, R. P., Eaton, J. W., Yu, S. H., and McKhann, C. F., 1982, Characterization of high and low metastatic clones derived from a methylcholanthrene induced murine fibrosarcoma. Cancer Research, 42, 1046–1051.

    Google Scholar 

  48. Wexler, H., 1966, Accurate identification of experimental pulmonary metastasis. Journal of the National Cancer Institute, 36, 641–643.

    Google Scholar 

  49. Wirl, G., 1977, Extractable collagenase and carcinogenesis of the mouse skin. Connective Tissue Research, 5, 171–178.

    Google Scholar 

  50. Wolf, B. A., and Goldberg, A. R., 1978, Lack of correlation between tumorigenicity and level of plasminogen activator in fibroblasts transformed by Rous sarcoma virus. Proceedings of the National Academy of Sciences USA, 75, 4967–4971.

    Google Scholar 

  51. Zimmerman, M., Quigley, J. P., Ashe, B., Dorn, C., Goldfarb, R., and Troll, W., 1978, Direct fluorescent assay of urokinase and plasminogen activators of normal and malignant cells: Kinetics and inhibitor profiles. Proceedings of the National Academy of Sciences, USA, 75, 750–753.

    Google Scholar 

Download references

Author information

Author notes

  1. Nancy Wang

    Present address: Department of Pathology, School of Medicine, Tulane University, 70112, New Orleans, LA, USA

Authors and Affiliations

  1. Department of Biochemistry, College of Biological Sciences, University of Minnesota, 55108, St. Paul, MN

    Mary E. H. McLaughlin & Irvin E. Liener

  2. Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, 55455, Minneapolis, MN, USA

    Nancy Wang

Authors
  1. Mary E. H. McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irvin E. Liener
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nancy Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

McLaughlin, M.E.H., Liener, I.E. & Wang, N. Proteolytic and metastatic activities of clones derived from a methylcholanthrene-induced murine fibrosarcoma. Clin Exp Metast 1, 359–371 (1983). https://doi.org/10.1007/BF00121198

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00121198

Keywords

Search

Navigation