Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Sep;70(3):506–512. doi: 10.1038/bjc.1994.336

Serum metalloproteinases and their inhibitors: markers for malignant potential.

T Baker 1, S Tickle 1, H Wasan 1, A Docherty 1, D Isenberg 1, J Waxman 1
PMCID: PMC2033376  PMID: 8080738

Abstract

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months' treatment with a gonadotrophin-releasing hormone agonist and an anti-androgen were analysed. Levels were compared with two control groups, comprising 21 patients with active rheumatoid arthritis and 56 age-matched hospital attenders without arthritis or cancer. Contrasting levels have been found in patients with prostatic cancer as compared with hospital controls without cancer and patients with rheumatoid arthritis. Patients with prostatic cancer had higher levels of TIMP-1 and collagenase (P = 0.0001) and lower levels of TIMP-2 (P = 0.003) than controls. Patients with metastatic cancer had significantly higher levels of collagenase than those without metastases (P = 0.02). Patients with rheumatoid arthritis had significantly higher levels of stromelysin than either controls (P = 0.002) or patients with cancer (P = 0.008). Serum tissue inhibitor of metalloproteinase 1 in combination with collagenase levels was as sensitive as prostate-specific antigen as a marker of metastatic disease. These findings provide a basis for the investigation of the role of metalloproteinases and their inhibitors in other malignancies.

Full text

PDF
506

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  2. Chowcat N. L., Savage F. J., Hembry R. M., Boulos P. B. Role of collagenase in colonic anastomoses: a reappraisal. Br J Surg. 1988 Apr;75(4):330–334. doi: 10.1002/bjs.1800750412. [DOI] [PubMed] [Google Scholar]
  3. Cooksley S., Hipkiss J. B., Tickle S. P., Holmes-Ievers E., Docherty A. J., Murphy G., Lawson A. D. Immunoassays for the detection of human collagenase, stromelysin, tissue inhibitor of metalloproteinases (TIMP) and enzyme-inhibitor complexes. Matrix. 1990 Oct;10(5):285–291. doi: 10.1016/s0934-8832(11)80183-6. [DOI] [PubMed] [Google Scholar]
  4. Docherty A. J., O'Connell J., Crabbe T., Angal S., Murphy G. The matrix metalloproteinases and their natural inhibitors: prospects for treating degenerative tissue diseases. Trends Biotechnol. 1992 Jun;10(6):200–207. doi: 10.1016/0167-7799(92)90214-g. [DOI] [PubMed] [Google Scholar]
  5. Garbisa S., Scagliotti G., Masiero L., Di Francesco C., Caenazzo C., Onisto M., Micela M., Stetler-Stevenson W. G., Liotta L. A. Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy. Cancer Res. 1992 Aug 15;52(16):4548–4549. [PubMed] [Google Scholar]
  6. Hembry R. M., Ehrlich H. P. Immunolocalization of collagenase and tissue inhibitor of metalloproteinases (TIMP) in hypertrophic scar tissue. Br J Dermatol. 1986 Oct;115(4):409–420. doi: 10.1111/j.1365-2133.1986.tb06235.x. [DOI] [PubMed] [Google Scholar]
  7. Hewitt R. E., Leach I. H., Powe D. G., Clark I. M., Cawston T. E., Turner D. R. Distribution of collagenase and tissue inhibitor of metalloproteinases (TIMP) in colorectal tumours. Int J Cancer. 1991 Nov 11;49(5):666–672. doi: 10.1002/ijc.2910490507. [DOI] [PubMed] [Google Scholar]
  8. Liotta L. A., Steeg P. S., Stetler-Stevenson W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991 Jan 25;64(2):327–336. doi: 10.1016/0092-8674(91)90642-c. [DOI] [PubMed] [Google Scholar]
  9. Lu X. Q., Levy M., Weinstein I. B., Santella R. M. Immunological quantitation of levels of tissue inhibitor of metalloproteinase-1 in human colon cancer. Cancer Res. 1991 Dec 1;51(23 Pt 1):6231–6235. [PubMed] [Google Scholar]
  10. Muller D., Wolf C., Abecassis J., Millon R., Engelmann A., Bronner G., Rouyer N., Rio M. C., Eber M., Methlin G. Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res. 1993 Jan 1;53(1):165–169. [PubMed] [Google Scholar]
  11. Murphy G., Cockett M. I., Stephens P. E., Smith B. J., Docherty A. J. Stromelysin is an activator of procollagenase. A study with natural and recombinant enzymes. Biochem J. 1987 Nov 15;248(1):265–268. doi: 10.1042/bj2480265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Murphy G., Koklitis P., Carne A. F. Dissociation of tissue inhibitor of metalloproteinases (TIMP) from enzyme complexes yields fully active inhibitor. Biochem J. 1989 Aug 1;261(3):1031–1034. doi: 10.1042/bj2611031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Poulsom R., Pignatelli M., Stetler-Stevenson W. G., Liotta L. A., Wright P. A., Jeffery R. E., Longcroft J. M., Rogers L., Stamp G. W. Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. Am J Pathol. 1992 Aug;141(2):389–396. [PMC free article] [PubMed] [Google Scholar]
  14. Pyke C., Ralfkiaer E., Huhtala P., Hurskainen T., Danø K., Tryggvason K. Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. Cancer Res. 1992 Mar 1;52(5):1336–1341. [PubMed] [Google Scholar]
  15. Stearns M. E., Wang M. Type IV collagenase (M(r) 72,000) expression in human prostate: benign and malignant tissue. Cancer Res. 1993 Feb 15;53(4):878–883. [PubMed] [Google Scholar]
  16. Stetler-Stevenson W. G., Brown P. D., Onisto M., Levy A. T., Liotta L. A. Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J Biol Chem. 1990 Aug 15;265(23):13933–13938. [PubMed] [Google Scholar]
  17. Talhouk R. S., Bissell M. J., Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 1992 Sep;118(5):1271–1282. doi: 10.1083/jcb.118.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Torti F. M. Response criteria in urologic malignancies. Recent Results Cancer Res. 1983;85:50–57. doi: 10.1007/978-3-642-81994-0_4. [DOI] [PubMed] [Google Scholar]
  19. Urbanski S. J., Edwards D. R., Maitland A., Leco K. J., Watson A., Kossakowska A. E. Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas. Br J Cancer. 1992 Dec;66(6):1188–1194. doi: 10.1038/bjc.1992.434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wagner S. N., Ruhri C., Kunth K., Holecek B. U., Goos M., Höfler H., Atkinson M. J. Expression of stromelysin 3 in the stromal elements of human basal cell carcinoma. Diagn Mol Pathol. 1992 Sep;1(3):200–205. [PubMed] [Google Scholar]
  21. Walakovits L. A., Moore V. L., Bhardwaj N., Gallick G. S., Lark M. W. Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury. Arthritis Rheum. 1992 Jan;35(1):35–42. doi: 10.1002/art.1780350106. [DOI] [PubMed] [Google Scholar]
  22. Waxman J., Sandow J., Thomas H., James N., Williams G. A pharmacological evaluation of a new 3-month depot preparation of buserelin for prostatic cancer. Cancer Chemother Pharmacol. 1989;25(3):219–220. doi: 10.1007/BF00689587. [DOI] [PubMed] [Google Scholar]
  23. Waxman J., Wasan H. The architecture of cancer. BMJ. 1992 Nov 28;305(6865):1306–1307. doi: 10.1136/bmj.305.6865.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zucker S., Wieman J., Lysik R. M., Imhof B., Nagase H., Ramamurthy N., Liotta L. A., Golub L. M. Gelatin-degrading type IV collagenase isolated from human small cell lung cancer. Invasion Metastasis. 1989;9(3):167–181. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES