EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN HUMAN PROSTATE

Purpose: Matrix metalloproteinase-7 (MMP-7), one of the extracellular matrix-degrading metalloproteinases, plays an important role in carcin oma invasion and metastasis. Tissue inhibitor metalloproteinase-1 (TIM P-1), one of the inhibitors of MMP-7, regulates extracellular matrix t urnover. Materials and Methods: Gene expression levels of MMP-7 and TI MP-1 were examined in 20 prostate carcinomas after hormonal therapy an d 12 benign prostate hyperplasias (BPH) by Northern blot analysis. Enz ymatic activities of MMP-7 were examined in 7 prostate carcinomas and 1 BPH in the above prostate tissues by the method of caseinolytic zymo graphy. These data were compared with the clinicopathological features . Results: There were significant correlations between levels of MMP-7 mRNA or the ratio of MMP-7 mRNA/TIMP-1 mRNA and pathological stage (p <0.01), lymph node metastasis (p <0.05), histological differentiation (p <0.05), vascular invasion (p <0.05), and lymphatic invasion (p <0. 05). Levels of MMP-7 mRNA and the ratio of MMP-7 mRNA/TlMP-1 mRNA were significantly increased in prostate carcinomas from patients with hig h levels of serum prostate specific antigen (PSA) (>10 ng./ml.) after hormonal therapy (p <0.05). The activation ratio of pro MMP-7 was elev ated in the cases with advanced prostate carcinoma compared with those of organ-confined prostate carcinoma and BPH. Conclusion: These resul ts suggest that MMP-7 may play an important role for invasion and meta stasis in prostate carcinomas, and the balance between MMP-7 and TIMP- 1 expression may relate to an invasive ability of prostate carcinomas.