Disease relevance of MMP7

• CONCLUSIONS: Our results confirm that increased MMP9 immunoreactivity in muscle fibres is a common feature of all inflammatory myopathies and suggest that MMP2 and MMP7 cannot be implicated in the inflammatory events of FM [1].
• RESULTS: MMP2 immunoreactivity was present in PM and dermatomyositis, MMP7 only in PM, and MMP9 in PM, dermatomyositis and FM [1].
• OBJECTIVES: The aim of our study was to investigate immunoexpression of matrix metalloproteinases MMP2, MMP7 and MMP9 in muscle specimens from patients with focal myositis (FM) vs polymyositis (PM) and dermatomyositis [1].
• CONCLUSIONS: We propose that the principle specificity for effective inhibitors of MMPs in pancreatic cancer should be for MMP-7 with secondary specificity against MMP-11 [2].
• Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer [3].
• This mutant and wild-type MMP-7 showed similar proteolytic activity toward fibronectin, whereas the mutant lacked the ability to induce the colon cancer cell aggregation [4].

Psychiatry related information on MMP7

• CONCLUSION: We conclude that measurement of plasma MMP-7 or MMP-9 levels, as performed in our trial, was not a useful prognostic or predictive factor in patients with MBC or in patients treated with an MMPI [5].

High impact information on MMP7

• Here we show that matrix metalloproteinase-7 (MMP-7) is expressed not only in the majority of human pancreatic ductal adenocarcinoma specimens, but also in human pancreatic intraepithelial neoplasia and metaplastic duct lesions in human and mouse [6].
• Under identical conditions, mice either deficient in MMP-7 or carrying an inactive FasL gene are severely inhibited in development of progressive metaplasia and acinar cell apoptosis [6].
• In a mouse model of pancreatic acinar-to-ductal metaplasia, MMP-7 progressively accumulates during the metaplastic transition, resulting in a concomitant increase in solubilization of Fas ligand (FasL) [6].
• Proliferation of gastric epithelial cells also was stimulated by MMP-7-treated myofibroblasts via IGF-II [7].
• We have studied the role of MMP-7 in signaling between epithelial cells and a key stromal cell type, the myofibroblast [7].

Chemical compound and disease context of MMP7

• In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally [8].
• MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded tissue sections of 94 rectal carcinomas were used for the immunohistochemical analysis of matrix metalloproteinases (MMP)-2, MMP-7, MT1-MMP, and tissue inhibitor of metalloproteinases (TIMP)-2 [9].
• PATIENTS AND METHODS: We measured plasma levels of MMP-7 and MMP-9 using an enzyme-linked immunoassay method in 140 evaluable patients with MBC enrolled on a multicenter clinical trial that compared the MMPI marimastat with placebo [5].
• Effect of an Efflux Pump Inhibitor on the Function of the Multidrug Efflux Pump CmeABC and Antimicrobial Resistance in Campylobacter [10].
• Nobiletin, a citrus flavonoid, down-regulates matrix metalloproteinase-7 (matrilysin) expression in HT-29 human colorectal cancer cells [11].

Biological context of MMP7

• However, Stat3 does not bind to the MMP7 promoter, but activates MMP7 gene expression indirectly via AP-1 [12].
• The promoter contains a Lef/Tcf consensus sequence, but using wildtype or Lef/Tcf-mutated promoter constructs, FGF-2-induced MMP7 reporter activity is independent from Lef/Tcf sites [12].
• Mapping of the metalloproteinase gene matrilysin (MMP7) to human chromosome 11q21-->q22 [13].
• We determined the chromosome location of the matrilysin gene (MMP7) by Southern and PCR analysis of two different panels of somatic cell hybrids and in situ hybridization of metaphase chromosomes [13].
• Our observations provide evidence that one mechanism whereby MMP-7 may promote tumor survival and resistance to doxorubicin is by cleaving FasL and reducing its effectiveness in triggering Fas-mediated apoptosis [14].

Anatomical context of MMP7

• MMP7 expression in normal pancreas and MMP7 and -11 expression in tumours was always seen the TIMP1 expression [15].
• We show that the angiogenic factor FGF-2 induces MMP7 expression in human endothelial cells [12].
• Matrilysin (MMP7) is a secreted matrix metalloproteinase, which contributes to angiogenesis by breaking down basement membranes [12].
• Thus, MMP-7 may act as a signal from epithelial cells for local recruitment of myofibroblasts and stimulation of their proliferation [16].
• Concanavalin A produces a matrix-degradative phenotype in human fibroblasts. Induction and endogenous activation of collagenase, 72-kDa gelatinase, and Pump-1 is accompanied by the suppression of the tissue inhibitor of matrix metalloproteinases [17].

Associations of MMP7 with chemical compounds

• Resistance to doxorubicin was also induced by expression in the tumor cells of constitutively active MMP-7 but not of a catalytically inactive mutant [14].
• MMP-7 can also activate proMMP-9 up to approximately 50% of the full activity with a new NH2 terminus of Leu16-Arg-Thr-(Asn)-Leu [18].
• Nitroglycerin 2,000 pmol also increased MMP-2 and MMP-7 mRNA levels to 187 +/- 8% and 183 +/- 21% of control values, respectively (p < 0.05) [19].
• Active pump-1 is inhibited by EDTA, 1,10-phenanthroline, and the tissue inhibitor of metalloproteinases [20].
• N-Acetyl-L-cysteine, superoxide (O2-) dismutase and catalase attenuated the EGCG-induced pro-MMP-7 production, suggesting an involvement of oxidative stress in these events [21].
• On the other hand, estrogen acidification of the luminal solution would tend to alkalinize exocytotic vesicles and may lead to decreased activation of the MMP-7 [22].

Physical interactions of MMP7

• Using EMSA analysis we also observed that the EGF stimulated increase in PEA3 transcription factors led to increased binding to specific ETS sites within the MMP-7 promoter [23].

Enzymatic interactions of MMP7

• MMP-7 (matrilysin) rapidly cleaved TFPI to a major 35-kDa product [24].
• MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn [25].
• MMP-7 efficiently cleaved recombinant FasL in vitro and reduced cell surface FasL expression [14].
• The activated MMP-9 products generated by MMP-26 appeared more stable than those cleaved by MMP-7 under the conditions tested [26].
• ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3 [27].

Regulatory relationships of MMP7

• Cyclin D1 was expressed in the nucleus and MMP7 was expressed in the cytoplasm in 26% and 75% of tumors, respectively [28].
• We also found that 6/8 MM cell lines expressed MMP-7 (matrilysin) and 3/8 MM cell lines expressed MMP-10 (stromelysin-2) [29].
• RESULTS: MMP-2 was mainly expressed in the stromal cells and MMP-7 showed their highest values in the epithelial cells [30].
• The results of the present study suggested that down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma [31].
• beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer [32].
• These results suggest that Fas downregulation and a consequential increased resistance to FasL-triggered apoptosis resulting from upregulated MMP-7 in colorectal cancer cells could be a key mechanism for their escape from the immune surveillance, thereby predicting a poor survival in CRC patients [33].

Other interactions of MMP7

• However, rates of cleavage were most rapid for MMP-7 and MMP-9 [24].
• Northern hybridization analyses revealed that ConA elevated the steady-state mRNA levels for MMPs; collagenase mRNA increased approximately 16-fold, MMP-2 increased 2-fold, and Pump-1, a recently described MMP gene, was induced [17].
• No binding to matrilysin (MMP-7) and collagenase 1 (MMP-1) was detected at inhibitor concentrations up to 60 microm [34].
• Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin) [35].
• (-)-Epigallocatechin-3-gallate promotes pro-matrix metalloproteinase-7 production via activation of the JNK1/2 pathway in HT-29 human colorectal cancer cells [21].

Analytical, diagnostic and therapeutic context of MMP7

• RT-PCR using a specific primer pair for MMP-7 demonstrated expression in 86% of the carcinoma tissue and in 57% of the control tissue samples [36].
• Active MMP-7 species of 19 kDa and its activity were demonstrated in the carcinoma samples with proMMP-7 production by immunoblotting and zymography, respectively [36].
• The expressions of MMP-7 were further confirmed by agarose gel electrophoresis and Western blotting [37].
• However, the relative expression level of MMP-7 was sequentially elevated when comparing Control, Kasai's Procedure and Liver Transplantation groups, and there was significant (P=0.019) difference when comparing Control and Liver Transplantation groups [37].
• Coculture of HIV-infected PBMCs with HMVEC-C increased MMP-1 (110-fold) and MMP-2 (307-fold) but not active MMP-7 and -9 [38].

References