Disease relevance of MMP25

• Taken these facts together, we conclude that MT6-MMP may participate in tumor invasion and metastasis by directly converting proMMP-2 into active form [1].
• On the basis of these results, we propose that MT6-MMP may facilitate tumor progression through its ability to activate progelatinase A at the membrane of cells from colon carcinomas or brain tumors [2].
• MT6-MMP was also detected at high levels in SW480 colon carcinoma cells as well as in some anaplastic astrocytomas and glioblastomas, but not in normal colon or brain or in meningiomas [2].
• These results show that MT6-MMP may play a role in colon cancer and exhibit unique biochemical and structural properties that may regulate proteolytic function at the cell surface [3].

High impact information on MMP25

• Using the catalytically inactive mutant MMP-2EA (the E404A mutant of proMMP-2), which cannot autocatalytically mature from the intermediate form into the mature one, we show that MT6-MMP cleaves not only the known MT-MMP-processing site at Asn(66)-Leu but also the previously unsuspected Asn(109)-Tyr to yield a fully mature molecule [1].
• Despite their difference in mediating proMMP-2 activation in transfected cells, the CAT of MT6-MMP appears to be as efficient as that of MT5-MMP in cleaving proMMP-2EA in buffer, suggesting that its CAT is a strong proMMP-2 activator [1].
• Based on these properties, this novel human matrix metalloproteinase has been called MT6-MMP because it is the sixth identified member of this subfamily of matrix metalloproteinase [2].
• Northern blot analysis of polyadenylated RNAs isolated from human tissues demonstrated that MT6-MMP is predominantly expressed in leukocytes, lung, and spleen [2].
• Cotransfection of expression plasmids encoding MT6-MMP and progelatinase A resulted in activation of COS-7-secreted progelatinase A, as demonstrated by gelatin zymography [2].

Biological context of MMP25

• We conclude that MMP-20 produced during primary dentinogenesis is incorporated into dentin and may be released during caries progression [4].

Anatomical context of MMP25

• MT6-MMP forming a complex with clusterin was detected in human neutrophils as well [5].
• Because clusterin is an abundant protein in the body fluid in tissues, it may act as a negative regulator of MT6-MMP in vivo [5].
• To explore the possible function of this domain, we purified a recombinant MT6-MMP with the hemopexin-like domain as a soluble form using a Madin-Darby canine kidney cell line as a producer [5].
• Our findings suggest that MT6-MMP could play a role in cellular migration and invasion of the extracellular matrix and basement membranes and its activity may be tightly regulated by all members of the TIMP family [6].
• Taken together, leukolysin may be part of the proteolytic arsenal deployed by leukocytes during inflammatory responses [7].

Associations of MMP25 with chemical compounds

• In addition, phosphatidyl inositol-specific phospholipase C treatment released MT6-MMP from the surface of transfected cells [8].
• Here, we show that alpha-1-proteinase inhibitor, or alpha1-PI, a known protective shield against destructive serine proteinases, is a physiological target for leukolysin [9].

Other interactions of MMP25

• The enzyme activity of the soluble MT6-MMP was inactive in the clusterin complex [5].
• Mature and soluble MT6-MMP processed at the furin motif was purified as a 45-kDa protein together with a 46-kDa protein having a single cleavage in the hemopexin-like domain [5].
• Our results showed that MT6-MMP as well as MT4-MMP were labeled with [3H]ethanolamine indicating the presence of a GPI unit with incorporated label [8].
• The proteolytic activity of MT6-MMP has been studied using recombinant catalytic fragments and shown to degrade several components of the extracellular matrix [5].
• Thus, we tested the possibility that MT6-MMP was also a GPI-anchored proteinase [8].

Analytical, diagnostic and therapeutic context of MMP25

• In immunohistochemistry, MMP-20-positive staining was observed most intensively in the radicular odontoblastic layer and also in dilated dentinal tubuli of caries lesions [4].
• By Western blotting, MMP-20 was detected in odontoblasts and pulp tissue of both sound and carious teeth, in dentinal fluid and dentin of sound teeth, but not in soft carious dentin [4].
• PCR primers for MMP-17, MMP-18, and MMP-20 were optimized for use in RT-PCR [10].

References