Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase‐20 in human cancers

Background Matrix metalloproteinases‐20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues. Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N‐linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20‐DSPP interaction in oral carcinogenesis. Methods This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms. Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts. Results Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts. Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers. DSPP expression increased significantly with tumor stage in all cancers examined. Conclusions The co‐localization and potential MMP20‐DSPP interaction previously reported in oral cancers are present in other cancers. These results suggest MMP20‐DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications. Our data provide a major reference and baseline document for studies on the role, mechanism, and significance of MMP20‐DSPP expression in major human epithelial neoplasms. In this respect, it is both significant and novel. Furthermore, future findings may offer new opportunities for intervention in epithelial cancers. For example, in cancers in which both MMP20 and its DSPP partner are upregulated, any synthetic MMP protease inhibitor that may be proposed to be used to treat the disorder should first be shown to work in the presence of MMP20 and DSPP.