Disease relevance of MMP17

• We have investigated the involvement of MT4-MMP, a glycosylphosphatidylinositol-anchored protease, in breast cancer progression [1].
• Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases [1].
• In contrast, quantitative reverse transcription-PCR analysis reveals similar MT4-MMP mRNA levels in human breast adenocarcinomas and normal breast tissues [1].
• Interestingly, immunohistochemical analysis shows that MT4-MMP production at protein level is strongly increased in epithelial cancer cells of human breast carcinomas compared with normal epithelial cells [1].
• MT4-MMP protein was also detected in nasal polyp eosinophils by immunohistochemistry [2].

High impact information on MMP17

• Deletion of the PEX domain in MT1-MMP, or swapping the domain with the one derived from MT4-MMP, abolished the ability to activate proMMP-2 on the cell surface without affecting the proteolytic activities [3].
• Positive staining for MT4-MMP is also detected in lymph node metastases [1].
• We provide for the first time evidence that MT4-MMP overproduction accelerates in vivo tumor growth, induces enlargement of i.t. blood vessels, and is associated with increased lung metastases [1].
• Stable transfection of MT4-MMP cDNA in human breast adenocarcinoma MDA-MB-231 cells does not affect in vitro cell proliferation or invasion but strongly promotes primary tumor growth and associated metastases in RAG-1 immunodeficient mice [1].
• MT4-MMP also contains a nine-residue insertion between the propeptide and the catalytic domain, which is a common feature of MT-MMPs and stromelysin-3 [4].

Biological context of MMP17

• Localization of the human membrane type 4-matrix metalloproteinase gene (MMP17) to chromosome 12q24 [5].
• Conversely, the SW480 transformants showed up-regulation of MMP12 and MMP17 [6].
• On the basis of these structural characteristics, this novel MMP has been tentatively called MT4-MMP, because it represents the fourth member of this subclass of MMPs characterized mainly by the occurrence of putative transmembrane domain in their amino acid sequences [4].
• Catalytic activities and substrate specificity of the human membrane type 4 matrix metalloproteinase catalytic domain [7].
• Membrane type 4 matrix metalloproteinase (MT4-MMP) shows the least sequence homology to the other MT-MMPs, suggesting a distinct function for this protein [8].

Anatomical context of MMP17

• MMP-2 and MMP-17 were also significantly represented in monocytes, although B cells had significant amounts of these MMPs [9].
• MT4-MMP mRNA was seen in both invasive and noninvasive HBC cell lines and was also not collagen-regulated, and MT2-MMP mRNA was not detected in any of the HBC cell lines tested [10].
• Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining [11].
• The expression of MT4-MMP in leukocytes together with its putative membrane localization suggest that this enzyme could be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators such as tumor necrosis factor-alpha [4].
• MT4-MMP was detected by Western blot in monocyte/macrophage cell lines which in combination with its fibrinolytic and TNFalpha-converting activity suggests a role in inflammation [8].

Associations of MMP17 with chemical compounds

• This hydrophobicity pattern is similar to glycosyl-phosphatidyl inositol (GPI)-anchored MMP, MT4-MMP, and other GPI-anchored proteins [12].

Physical interactions of MMP17

• The progelatinase A/TIMP-2 complex that usually reacts like TIMP-2 also inhibits MT4-MMP [13].

Other interactions of MMP17

• MT3- and MT4-MMP mRNA expressions were significantly higher in hEMVECs than in hFMVECs [14].
• We have found that MT6-MMP is closer in function to stromelysin-1 than MT1 and MT4-MMP in terms of substrate and inhibitor specificity, being able to cleave type-IV collagen, gelatin, fibronectin and fibrin [15].
• Its activity towards synthetic peptide substrates, components of the extracellular matrix and inhibitors of MMPs was studied and compared with MT1-MMP, MT4-MMP and stromelysin-1 [15].
• Stimulation of eosinophils with TNF-alpha increased MT4-MMP mRNA expression [2].
• TIMP-2, a strong inhibitor of other MT-MMPS, inhibits MT4-MMP at low concentrations [13].

Analytical, diagnostic and therapeutic context of MMP17

• Northern blot analysis of polyadenylated RNAs isolated from a variety of human tissues revealed that the MT4-MMP gene (MMP-17) is expressed mainly in the brain, leukocytes, the colon, the ovary, and the testis [4].
• The constitutive expression of MT4-MMP mRNA was detected by RT-PCR in unstimulated eosinophils, lymphocytes, and monocytes, but not neutrophils [2].
• PCR primers for MMP-17, MMP-18, and MMP-20 were optimized for use in RT-PCR [16].
• Furthermore, cell surface biotinylation and indirect immunofluorescence show that transiently expressed MT1-MT4-MMP chimaeras failed to reach the plasma membrane and were retained in the endoplasmic reticulum [17].

References