Matrix Metalloproteinase 20–Dentin Sialophosphoprotein Interaction in Oral Cancer
| Autor: | Geetu Saxena, Kalu U.E. Ogbureke, Komal Koli, J. De La Garza |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Keratinocytes
Bone sialoprotein Cytoplasm Pathology medicine.medical_specialty Transcription Genetic Sialoglycoproteins Matrix metalloproteinase stomatognathic system Dentin sialophosphoprotein Western blot Cell Line Tumor medicine Dentin Humans Integrin-Binding Sialoprotein Osteopontin Promoter Regions Genetic General Dentistry Cell Nucleus Extracellular Matrix Proteins medicine.diagnostic_test biology Chemistry Phosphoproteins Dentin phosphoprotein Molecular biology stomatognathic diseases Matrix Metalloproteinase 20 medicine.anatomical_structure Matrix Metalloproteinase 9 Carcinoma Squamous Cell biology.protein Matrix Metalloproteinase 2 Matrix Metalloproteinase 3 Mouth Neoplasms Precancerous Conditions Dentin sialoprotein |
| Zdroj: | Journal of Dental Research. 94:584-593 |
| ISSN: | 1544-0591 0022-0345 |
| DOI: | 10.1177/0022034515570156 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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