Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of members of the family of matrix-degrading metalloproteinases (MMPs) is believed to contribute to the complex process of invasion and metastasis. In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)--were used to examine the expression of these three different MMPs in human gastric and colonic carcinomas and in adjacent normal mucosa. The expression of pump-1 mRNA in malignant colon and stomach samples was striking. In a total of 10 gastric carcinoma samples examined, eight (80%) expressed pump-1 transcripts; similarly, 6 of 8 (75%) colon carcinoma samples were also positive. Stromelysin and stromelysin-2 mRNAs were not detected in any of these samples. Expression of the MMPs examined was not detected in any of the adjacent, grossly normal tissue samples. Using in situ hybridization and affinity purified anti-pump-1 antibodies, the expression of pump-1 mRNA and protein was localized to tumor cells and was not detected in stromal or lymphocytic cells. This data suggests that the inappropriate expression of pump-1 by malignant cells may contribute to the neoplastic phenotype.
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PMID:Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas. 179 90

Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of colon carcinoma and many other human cancers. The present study demonstrates that treatment of human colon carcinoma cells with active matrilysin induces cell aggregation in vitro and promotes liver metastasis in nude mice. When two kinds of colon carcinoma cell lines were incubated with active matrilysin, this enzyme efficiently bound to the cell surface and induced loose cell aggregation, which led to E-cadherin-mediated tight cell aggregation. Synthetic MMP inhibitors inhibited both the membrane binding of matrilysin and matrilysin-induced cell aggregation, while TIMP-2 inhibited only the cell aggregation. Two other active MMPs, stromelysin and gelatinase A, neither bound to cell membrane nor induced cell aggregation. Tumor cells in loose cell aggregates could reaggregate even after they were freed from matrilysin and dispersed. When injected into the spleen of nude mice, the tumor cells in the stable aggregates produced much larger metastatic nodules in the livers than control cells and those in the loose aggregates. These results suggest that matrilysin may enhance metastatic potential of tumor cells by processing a cell surface protein(s) and thereby inducing loose and then tight aggregation of tumor cells.
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PMID:Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and enhances their metastatic potential in nude mouse model. 1464 60

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in colorectal carcinomas (CRCs). Here, we define the relationship between STAT3 function and the malignant properties of colon carcinoma cells. Elevated activation of STAT3 enhances invasive growth of the CRC cell lines. To address mechanisms through which STAT3 influences invasiveness, the protease mRNA expression pattern of CRC biopsies was analyzed and correlated with the STAT3 activity status. These studies revealed a striking coincidence of STAT3 activation and strong expression of matrix metalloproteinases MMP-1, -3, -7, and -9. Immunohistological examination of CRC tumor specimens showed a clear colocalization of MMP-1 and activated STAT3. Experimentally induced STAT3 activity in CRC cell lines enhanced both the level of MMP-1 mRNA and secreted MMP-1 enzymatic activity. A direct connection of STAT3 activity and transcription from the MMP-1 promoter was shown by reporter gene experiments. Moreover, high-affinity binding of STAT3 to STAT recognition elements in both the MMP-1 and MMP-3 promoter was demonstrated. Xenograft tumors arising from implantation of CRC cells into nude mice showed simultaneous appearance and colocalization of p-Y-STAT3 and MMP-1 expression. Our results link aberrant activity of STAT3 in CRC to malignant tumor progression through upregulated expression of MMPs.
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PMID:Signal transducer and activator of transcription 3 activation promotes invasive growth of colon carcinomas through matrix metalloproteinase induction. 1746 Jul 72