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

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114 Citations (Scopus)

Abstract

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
Volume53
Issue number19
StatePublished - Jan 1 1993
Externally publishedYes

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Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase Inhibitors
Prostate
Conditioned Culture Medium
Matrix Metalloproteinase 2
Gelatinases
Serum-Free Culture Media
Matrix Metalloproteinase 9
Enzyme Assays
Collagenases
Gelatin
Matrix Metalloproteinases
Epithelial Cells
Neoplasm Metastasis
Carcinoma
Neoplasms
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "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",
abstract = "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.",
author = "Lokeshwar, {Balakrishna L} and Selzer, {Marie G.} and Miami Block and Zeenat Gunja-Smith",
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T1 - Secretion of Matrix Metalloproteinases and Their Inhibitors (Tissue Inhibitor of Metalloproteinases) by Human Prostate in Explant Cultures

T2 - Reduced Tissue Inhibitor of Metalloproteinase Secretion by Malignant Tissues

AU - Lokeshwar, Balakrishna L

AU - Selzer, Marie G.

AU - Block, Miami

AU - Gunja-Smith, Zeenat

PY - 1993/1/1

Y1 - 1993/1/1

N2 - 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.

AB - 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.

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