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Secretion of Matrix Metalloproteinases and Their Inhibitors (Tissue Inhibitor of Metalloproteinases) by Human Prostate in Explant Cultures: Reduced Tissue Inhibitor of Metalloproteinase Secretion by Malignant Tissues¹

Department of Urology [B. L. L., M. G. S., N. L. B.] and Medicine [Z. G-S.], University of Miami School of Medicine, Miami, Florida 33101

² To whom requests for reprints should be addressed, at Department of Urology (M-800), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101.

Unregulated secretion of matrix metalloproteinases (MMPs) or their endogenous protein inhibitors (tissue inhibitor of metalloproteinases, TIMPs) has been implicated in tumor invasion and metastasis. Species of MMPs and TIMPs secreted by epithelial cultures of normal, benign, and malignant prostate were identified and their levels were compared. Fragments of fresh tissue were cultured in a serum-free medium that supported the outgrowth of prostatic epithelial cells. Biochemical analysis of the conditioned media by gelatin zymography and enzyme assays showed that both normal and neoplastic tissues secreted latent and active forms of both M_r 72,000 type IV collagenase (MMP-2) and M_r 92,000 gelatinase (MMP-9). However, conditioned media from malignant prostate explants contained a higher proportion of the active form of MMP-2. Significant amounts of free TIMPs were secreted by normal juvenile and adult prostates, but they were either markedly reduced or not detectable in conditioned media from neoplastic tissues. These findings suggest that there is an imbalance of secretion between MMPs and TIMPs in prostatic carcinoma.

¹ This work was supported in part by the Weeks Endowment Fund, Department of Urology, University of Miami, Veterans Administration Merit Review (N. L. B. and B. L. L.), American Heart Association, Florida Affiliate, and the NIH Grant No. AR16940 (Z. G-S.).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 3/15/93. Accepted 7/28/93.

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