Disease relevance of MMP16

• MT3-MMP co-immunoprecipitated with MCSP in WM1341D melanoma cells cultured on type I collagen or laminin [1].
• Although the sample size was small, it was evident that MT3-MMP mRNA expression in clear cell subtype renal cell carcinomas was higher than in the group of tumors including the granular cell subtype [2].
• It is interesting that the expression of MT3-MMP was higher in carcinomas, especially clear cell carcinoma, than in normal parenchyma, so that MT3-MMP may provide a clue an understanding of the molecular mechanism of carcinogenesis in human kidney [2].
• Regarding their localization, MT1- and MT2-MMPs were found in alveolar epithelial cells, MT3-MMP in fibroblasts from fibroblastic foci and alveolar epithelial cells and MT5-MMP in basal bronchiolar epithelial cells and in areas of squamous metaplasia [3].
• RESULTS: The expressions of MT1, MT2, and MT3-MMP were significantly higher in laryngeal cancer tissues than those in para-tumorous tissues (P < 0.01) and had a close relationship with invasive depth (P < 0.05) [4].

High impact information on MMP16

• beta-Catenin/Wnt signaling regulates expression of the membrane type 3 matrix metalloproteinase in gastric cancer [5].
• Up-regulation of MT3-MMP is critical to the invasive phenotype as shown by small interfering RNA (siRNA) studies [5].
• This study shows that the introduction of mutant beta-catenin into gastric cancer cell lines by adenoviral infection enhances invasiveness and proliferation and up-regulates the expression of the gene encoding the matrix metalloproteinase (MMP) family member membrane type 3 MMP (MT3-MMP) [5].
• Immunoprecipitation analysis demonstrated direct interaction of N-Tes with either MT1-MMP or MT3-MMP [6].
• Northern blot analysis demonstrated the predominant expression of MT1-MMP mRNA in carcinoma tissues (20 of 20 cases), whereas MT2-MMP was detected in only 25% of the cases (5 of 20 cases), and no detectable expression of MT3-MMP was observed [7].

Biological context of MMP16

• In contrast to the genes for many MMPs that are clustered on chromosome 11, the genes MMP14, MMP15, and MMP16 all map to distinct chromosomes [8].
• We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat [9].
• Furthermore, the elevated expression of MT1-MMP and MT3-MMP in SMCs was well associated with their dedifferentiated phenotype [10].
• In lung fibroblasts, TGF-beta1 induced a strong upregulation of MT3-MMP, both at the gene and protein level [3].

Anatomical context of MMP16

• Membrane type 3 matrix metalloproteinase (MT3-MMP), an activator for the zymogen of MMP-2 (proMMP-2, or progelatinase A), is known to be expressed in human placenta, brain, lung and rat vascular smooth muscle cells, but information about its biochemical properties is limited [11].
• Expression of MT3-MMP mRNA was seen in fibroblasts and some macrophages [12].
• Involvement of membrane-type matrix metalloproteinases (MT-MMPs) in capillary tube formation by human endometrial microvascular endothelial cells: role of MT3-MMP [13].
• To investigate the roles of the MT-MMPs in the matrix remodeling of blood vessels, expression of MT1-MMP and MT3-MMP was examined in normal and balloon-injured rat carotid arteries by in situ hybridization and immunohistochemistry [10].
• MT1-MMP mRNA was expressed in 8 cell lines, while MT2-MMP and MT3-MMP mRNAs were expressed in fewer cell lines [14].

Associations of MMP16 with chemical compounds

• The association between MT3-MMP and MCSP was largely disrupted by removing chondroitin sulfate glycosaminoglycan (CS) from the cell surface, suggesting CS could mediate the association between the two cell surface core proteins [1].
• There was a general higher expression of all MT-MMPs except for MT3-MMP in the androgen-insensitive cells DU 145 and PC-3 compared with that in the androgen-sensitive LNCaP cells [15].
• Effect of Losartan on the mRNA Expressions of MT3-MMP and TIMP-2 in Diabetic Kidneys [16].

Enzymatic interactions of MMP16

• The recombinant APP protein was cleaved by MT3-MMP in vitro at the A(463)-M(464), N(579)-M(580), H(622)-S(623), and H(685)-Q(686) peptide bonds, which included a cleavage site within the amyloid beta peptide region known to produce a C-terminal fragment [17].

Regulatory relationships of MMP16

• The results indicate that MT3-MMP possesses the potential to promote melanoma invasion and proteolysis and that the formation of a complex between MT3-MMP and MCSP may be a crucial step in activating these processes [1].
• Shedding of syndecan-1 was also induced by MT3-MMP but not by other MT-MMPs [18].

Other interactions of MMP16

• Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features [9].
• Recombinant syndecan-1 core protein was shown to be cleaved by recombinant MT1-MMP or MT3-MMP preferentially at the Gly245-Leu246 peptide bond [18].
• Among the MT-MMPs tested, MT3-MMP and MT5-MMP also caused efficient APP shedding [17].
• The 8q21.2 breakpoint is within MMP16 which encodes matrix metalloproteinase 16 [19].

Analytical, diagnostic and therapeutic context of MMP16

• In the present study of both non-neurological and Alzheimer brain tissues, we examined the localization of MT3-MMP by immunohistochemistry [20].
• Reverse transcriptase-polymerase chain reaction for MT3-MMP mRNA showed the same amount of expression in gray and white matters, while that for gelatinase A and MT1-MMP mRNA expressed much higher in the white matter than in the gray matter [20].
• Assignment of the human genes for membrane-type-1, -2, and -3 matrix metalloproteinases (MMP14, MMP15, and MMP16) to 14q12.2, 16q12.2-q21, and 8q21, respectively, by in situ hybridization [21].
• Cultured human monocyte-derived Mphi constitutively expressed MT3-MMP mRNA and proteolytically active protein, as demonstrated by mRNA analyses, immunoblotting, and gelatin zymography, respectively [22].
• Confocal microscopy and flow cytometry confirmed induction and spatial distribution of MT3-MMP protein from intracellular domains to the Mphi plasma membrane by Ox-LDL, tumor necrosis factor-alpha, or macrophage colony-stimulating factor [22].

References