SERUM METALLOPROTEINASES AND THEIR INHIBITORS - MARKERS FOR MALIGNANTPOTENTIAL

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result fro m 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 inhibito rs of metalloproteinase (TIMP) 1 and 2, which have allowed the study o f serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months' treatment with a g onadotrophin-releasing hormone agonist and an anti-androgen were analy sed. Levels were compared with two control groups, comprising 21 patie nts with active rheumatoid arthritis and 56 age-matched hospital atten ders without arthritis or cancer. Contrasting levels have been found i n patients with prostatic cancer as compared with hospital controls wi thout cancer and patients with rheumatoid arthritis. Patients with pro static 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 m etastatic cancer had significantly higher levels of collagenase than t hose 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 disea se. These findings provide a basis for the investigation of the role o f metalloproteinases and their inhibitors in other malignancies.