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 Tissues

Balakrishna L. Lokeshwar, Marie G. Selzer, Miami Block, Zeenat Gunja-Smith

Research output: Contribution to journalArticle

114 Scopus citations


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 Mr 72,000 type IV collagenase (MMP-2) and Mr 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.

Original languageEnglish (US)
Pages (from-to)4493-4498
Number of pages6
JournalCancer Research
Issue number19
StatePublished - Oct 1993
Externally publishedYes


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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