Tissue inhibitor of metalloproteinase-3 is a basement membrane-associated protein that is significantly decreased in human colorectal cancer Journal Article
| Authors: | Zeng, Z. S.; Sun, Y.; Shu, W. P.; Guillem, J. G. |
| Article Title: | Tissue inhibitor of metalloproteinase-3 is a basement membrane-associated protein that is significantly decreased in human colorectal cancer |
| Abstract: | PURPOSE: The balance between local levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases is believed to play a key role in tumor invasion and metastases. Because tissue inhibitor of metalloproteinase-3 suppresses tumorigenicity and tumor invasion in vitro, the aim of this study was to determine its expression in human colorectal cancer. METHODS: Thirty-nine human colorectal cancer specimens, three adenomas, and matched normal adjacent mucosa from 39 colorectal cancer patients were analyzed. Tissue inhibitor of metalloproteinase-3 ribonucleic acid and protein expression were analyzed by Northern blot hybridization and Western blot analysis, respectively. The cellular localizations of tissue inhibitor of metalloproteinase-3 ribonucleic acid and protein were determined by in situ hybridization and immunolocalization. RESULTS: Tissue inhibitor of metalloproteinase-3 ribonucleic acid expression was increased in colorectal cancer compared with paired normal mucosa. In contrast, tissue inhibitor of metalloproteinase-3 protein level was higher in normal mucosa than in the corresponding colorectal cancer. In addition, tissue inhibitor of metalloproteinase-3 protein levels progressively decreased with advancing colorectal cancer stages. Tissue inhibitor of metalloproteinase-3 protein tumor to normal mucosa ratio was 0.74 ± 0.12, 0.51 ± 0.18, 0.48 ± 0.12, and 0.45 ± 0.2 for Dukes A (n = 8), B (n = 9), C (n = 9), and D (n = 13) stages, respectively. Both tissue inhibitor of metalloproteinase-3 messenger ribonucleic acid and protein were located predominantly within spindle-shaped and round stromal cells. Furthermore, in colonic epithelium, tissue inhibitor of metalloproteinase-3 and type IV collagen protein were similarly concentrated in the basal region. CONCLUSIONS: These data provide the first detailed description of the cellular expression of tissue inhibitor of metalloproteinase-3 in colorectal cancer and identify it as a basement membrane-associated protein. This is an important observation, because the presence of tissue inhibitor of metalloproteinase-3 protein near the basement membrane supports its role in preventing proteolytic degradation, angiogenesis, and apoptosis. |
| Keywords: | adult; clinical article; human tissue; protein expression; aged; aged, 80 and over; middle aged; advanced cancer; cancer staging; colorectal cancer; adenocarcinoma; metastasis; apoptosis; protease inhibitors; basement membrane; protein degradation; angiogenesis; neovascularization, pathologic; colorectal neoplasms; cancer invasion; blotting, western; gene expression regulation, neoplastic; adenoma; membrane protein; blotting, northern; tissue inhibitor of metalloproteinase; matrix metalloproteinases; carcinogenic activity; correlation function; humans; human; male; female; article; tissue inhibitor of metalloproteinase-3; stromelysin inhibitor |
| Journal Title: | Diseases of the Colon and Rectum |
| Volume: | 44 |
| Issue: | 9 |
| ISSN: | 0012-3706 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2001-09-01 |
| Start Page: | 1290 |
| End Page: | 1296 |
| Language: | English |
| PUBMED: | 11584202 |
| PROVIDER: | scopus |
| DOI: | 10.1007/bf02234786 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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