title: Podoplanin is a novel myoepithelial cell marker in pleomorphic adenoma and other salivary gland tumors with myoepithelial differentiation.
abstract: The expression of podoplanin, one of the representative immunohistochemical markers for lymphatic endothelium, is upregulated in various kinds of cancers. Based on our previous studies, we have developed a hypothesis that podoplanin plays a role in cell adhesion via its association with extracellular matrix (ECM). Since salivary pleomorphic adenoma is histologically characterized by its ECM-enriched stroma, we firstly wanted to explore the expression modes of podoplanin in pleomorphic adenoma and related salivary tumors by immunohistochemistry. In normal salivary gland, podoplanin was specifically localized in myoepithelial cells, which were also positively labeled by antibodies against P63, of the intercalated duct as well as acini. In pleomorphic adenoma, podoplanin was colocalized with P63 and CD44 in basal cells of glandular structures as well as in stellate/spindle cells in myxochondroid matrices, where perlecan and hyaluronic acid were enriched. The expression of podoplanin was confirmed at both protein and mRNA levels in pleomorphic adenoma cell systems (SM-AP1 and SM-AP4) by using immunofluorescence, western blotting, and reverse transcription polymerase chain reaction. Podoplanin was localized on the cell border as well as in the external periphery of the cells. Moreover, podoplanin expression was also confirmed in tumor cells with myoepithelial differentiation in myoepithelioma and intraductal papilloma. The results indicate that podoplanin can be regarded as a novel myoepithelial marker in salivary gland tumors and suggest that podoplanin's communication with ECM molecules is essential to phenotypic differentiation to myoepithelial cells.
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsuneki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Ahmed
authors.initials: A
authors.lastname: Essa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abé
authors.forename: Hamzah Ali
authors.initials: HA
authors.lastname: Babkair
authors.forename: Md Shahidul
authors.initials: MS
authors.lastname: Ahsan
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D008949:Adenoma, Pleomorphic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002454:Cell Differentiation; D005455:Fluorescent Antibody Technique; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D009208:Myoepithelioma / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin