Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical studies using a polyclonal antibody, raised against the recombinant form of dentin matrix protein 1 (DMP1), show that DMP1 was detected mainly in odontoblasts in cultured mouse embryonic tooth germs. However, in restricted areas, DMP1 staining was also observed in secretory ameloblasts, in the stratum intermedium and stellate reticulum, but only when the odontoblasts located in front of them were unstained. When the embryonic tooth germs were cultured in the presence of inositol hexasulfate, a casein kinase I and II inhibitor, staining of odontoblasts was weak or nil, whereas, in contrast, ameloblasts and enamel organ were strongly immunolabelled, suggesting an enhanced translocation of DMP1 after secretion to the secretory ameloblasts and/or stratum intermedium and stellate reticulum. Moreover, DMP1--was shown to be a good substrate for gelatinase A (MMP-2), but not to gelatinase B (MMP- 9). We hypothesized that DMP1--or the sub-fractions cleaved by the MMP--could behave as diffusible signaling molecule (s) rather than as a true dentin extracellular matrix component.
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PMID:Inositol hexasulphate, a casein kinase inhibitor, alters the distribution of dentin matrix protein 1 in cultured embryonic mouse tooth germs. 1145 52

Various combinations of the SIBLING family of proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p<0.0001), BSP and MMP-3 (p<0.0001), and OPN and MMP-3 (p<0.0024). We conclude that BSP, DSPP, and OPN are highly up-regulated in OSCC. While the production of these SIBLINGs is independent of T, they correlate with oral location of tumor, cognate MMP expression, and for DSPP, the degree of tumor differentiation.
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PMID:Up-regulation of SIBLING proteins and correlation with cognate MMP expression in oral cancer. 1730 12

Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. However, the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are yet to be identified. Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis.
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PMID:Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer. 2566 17

We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons.
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PMID:Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. 2766 30