Wnt Signaling and Histological Characteristics of Odontogenic Tumors*Corresponding Author:
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We have reviewed our studies on Notch signaling of oral neoplasms in the International Journal of Molecular Science. We examined Notch signaling via immunohistochemistry in cases of ameloblastoma, ameloblastic carcinoma, calcifying epithelial odontogenic tumors, squamous odontogenic tumors, ameloblastic fibroma, odontogenic myxoma, and calcifying odontogenic cysts. In epithelial tumors, Notch-positive staining products were frequently detected in epithelial tumor nests, especially in differentiating cells. In mixed epithelial and mesenchymal tumors, Notch-positive products were present in both the epithelial and ectomesenchymal components. In mesenchymal tumors, Notch-positive products were not detected. In cases of odontogenic carcinoma, products strongly positive for Notch were detected in most neoplastic cells. Positive reactions tended to be strong in areas with high proliferating activity.
In our investigation, we suggest that Notch signaling plays a role in cytological differentiation, epithelial-mesenchymal interaction, formation of tumor stroma, and acquisition of tissue specific characteristics in neoplastic cells of tooth enamel organ-derived neoplasms, including benign and malignant neoplasms. Our previous studies demonstrated that Jagged is a major Notch ligand expressed on odontogenic tumors. Therefore, Notch signaling in odontogenic tumorigenesis is thought to be triggered by Jagged-Notch signaling. Jagged-Notch signaling is involved in hard tissue formation in tooth development. This signaling is also inherited in tumorigenesis and may be related to acquisition of the characteristics of odontogenic tumors.
In tooth development, the Bmp, Fgf, Shh, Wnt and Notch pathways act as major signaling pathways and are involved in imparting organ-specific features. Wnt signaling modulates diverse cellular processes during embryogenesis and histogenesis. In addition, deregulation of Wnt signaling has been implicated in tumorigenesis and progression. It is known that Wnt signaling plays fundamental roles in odontogenesis through epithelial-mesenchymal interactions; this interaction is thought to directly reflect the development of odontogenic neoplasms. Our review also conveys that Wnt signaling may be involved in tumor cell differentiation of odontogenic tumors. Therefore, we additionally examined Wnt signaling molecules in odontogenic tumors.