Metastatic potential correlates with enzymatic degradation of basement membrane collagen (original) (raw)

Nature volume 284, pages 67–68 (1980)Cite this article

Abstract

Tumour cells traverse epithelial and endothelial basement membranes during the successive stages of the metastatic process. At the transition from in situ to invasive carcinoma, local dissolution of the basement membrane is observed microscopically1,2, and coincides with tumour cell invasion of the underlying stroma. Tumour cells further traverse the endothelial basement membrane during entry into and egress from blood vessels3–5. Electron microscopic studies have shown local dissolution of basement membrane at its area of contact with invading tumour cells, suggesting an enzymatic mechanism3,6,7. Basement membranes are resilient structures which present a mechanical barrier to invasion8. Type IV collagen is a major structural protein of basement membranes and is chemically and genetically distinct from stroma collagen types I and III and cartilage collagen type II9,10. Previously characterised animal collagenases which cleave collagen types I; II and III fail to degrade type IV collagen11,12. We have recently purified about 1,000-fold and characterised a neutral protease activity preferential for type IV collagen from metastatic tumour cells and shown that it (1) produces specific degradation products, (2) has a molecular weight of 65,000, (3) is not plasmin or a cathepsin, by _p_H and inhibitor studies, and (4) does not significantly degrade other collagens or fibronectin12,13. Here we extend the relevance of this finding by quantitating the ability of several murine tumour cell lines of known metastatic potential to degrade type IV collagen. The cell lines with the highest incidence of spontaneous metastasis exhibit the greatest level of type IV collagen-degrading activity in two different assays using either living cells or media obtained from cell cultures.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Ozello, L. Am. J. Path. 35, 887–899 (1959).
    Google Scholar
  2. Rubio, C. A. & Biberfeld, P. Acta path. microbiol. scand. A83, 744–748 (1975).
    CAS Google Scholar
  3. Vlaeminck, M. N., Adenis, L., Mouton, Y. & Demaille, A. Int. J. Cancer 10, 619–631 (1972).
    Article CAS Google Scholar
  4. Roos, E. & Dingemans, K. P. Biochim. biophys. Acta 560, 135–166 (1979).
    CAS PubMed Google Scholar
  5. Liotta, L. A., Kleinerman, J., Catanzaro, D. & Rynbrandt, D. J. natn. Cancer Inst. 58, 1427–1431 (1977).
    Article CAS Google Scholar
  6. McKinney, R. & Singh, B. Oral Surg. 44, 875–888 (1977).
    Article Google Scholar
  7. Babai, F. J. ultrastruct. Res. 56, 287–303 (1976).
    Article CAS Google Scholar
  8. Vracko, R. Am. J. Path. 77, 314–346 (1974).
    CAS PubMed Google Scholar
  9. Kefalides, N. A. Int. Rev. connective Tissue Res. 6, 63–104 (1973).
    Article CAS Google Scholar
  10. Kefalides, N. A. Biochem. biophys. Res. Commun. 45, 226–234 (1971).
    Article CAS Google Scholar
  11. Wooley, D. E., Glanville, R. W., Roberts, D. R. & Evanson, J. M. Biochem. J. 169, 265–276 (1978).
    Article Google Scholar
  12. Liotta, L. A., Abe, S., Gehron Robey, P. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 76, 2268–2272 (1979).
    Article ADS CAS Google Scholar
  13. Liotta, L. A., Garbisa, S., Tryggvason, K., Gehron-Robey, P. & Martin, G. R. Am. Ass. Cancer Res. Proc. 17th A. Meet. 235 (1979).
  14. Fidler, I. J. Nature new Biol. 242, 148–149 (1973).
    Article CAS Google Scholar
  15. Fidler, I. J. & Kripke, M. L. Science 197, 893–895 (1977).
    Article ADS CAS Google Scholar
  16. Liotta, L. A., Vembu, D., Saini, R. & Boone, C. J. natn. Cancer Inst. 38, 1231–1236 (1978).
    CAS Google Scholar
  17. Boone, C. W., Takeichi, N., Eaton, S. & Paranjpe, M. Science 204, 177–179 (1979).
    Article ADS CAS Google Scholar
  18. Orkin, R. W. et al. J. exp. Med. 145, 204–220 (1977).
    Article CAS Google Scholar
  19. Timpl, R., Martin, G. R., Bruckner, P., Wick, G. & Weidemann, H. Eur. J. Biochem. 84, 43–52 (1978).
    Article CAS Google Scholar
  20. Garbisa, S., Tryggvason, K., Foidart, J. M. & Liotta, L. A. (submitted).
  21. Nicolson, G. L. Scient. Am. 240, 66–76 (1979).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Laboratory of Pathophysiology, National Cancer Institute,
    L. A. Liotta, S. Garbisa & S. Shafie
  2. Fredrick Cancer Research Center, National Cancer Institute,
    Ian Hart
  3. Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research,
    K. Tryggvason
  4. Laboratory of Chemistry, National Institute of Arthritis, Metabolism and Digestive Diseases, National Institutes of Health, Bethesda, Maryland, 20205
    C. M. Foltz

Authors

  1. L. A. Liotta
    You can also search for this author inPubMed Google Scholar
  2. K. Tryggvason
    You can also search for this author inPubMed Google Scholar
  3. S. Garbisa
    You can also search for this author inPubMed Google Scholar
  4. Ian Hart
    You can also search for this author inPubMed Google Scholar
  5. C. M. Foltz
    You can also search for this author inPubMed Google Scholar
  6. S. Shafie
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Liotta, L., Tryggvason, K., Garbisa, S. et al. Metastatic potential correlates with enzymatic degradation of basement membrane collagen.Nature 284, 67–68 (1980). https://doi.org/10.1038/284067a0

Download citation

This article is cited by