Aberrant Gene Expression in Epithelial Cells of Mixed Odontogenic Tumors

Abstract

Comparative investigations of odontogenic cells in normally forming teeth and tumors may provide insights into the mechanisms of the differentiation process. The present study is devoted to late phenotypic markers of ameloblast and odontoblast cells, i.e., proteins involved in biomineralization. The in situ expression of amelogenins, keratins, collagens type III and IV, vimentin, fibronectin, osteonectin, and osteocalcin was performed on normal and tumor odontogenic human cells. The pattern of protein expression showed some similarities between ameloblasts and odontoblasts present in normally developing human teeth and cells present in neoplastic tissues of ameloblastic fibroma, ameloblastic fibro-odontomas, and complex odontomas. Amelogenins (for ameloblasts) and osteocalcin (for odontoblasts) were detected in cells with well-organized enamel and dentin, respectively. In contrast, "mixed" cells located in epithelial zones of mixed odontogenic tumors co-expressed amelogenins and osteocalcin, as shown by immunostaining. The presence of osteocalcin transcripts was also demonstrated by in situ hybridization in these cells. Keratins and vimentin were detected in the same epithelial zones. Tumor epithelial cells were associated with various amounts of polymorphic matrix (amelogenin- and osteocalcin-immunoreactive), depending on the types of mixed tumors. No osteocalcin labeling was found in epithelial tumors. This study confirms that the differentiation of normal and tumor odontogenic cells is accompanied by the expression of some common molecules. Furthermore, the gene products present in normal mesenchymal cells were also shown in odontogenic tumor epithelium. These data may be related to a tumor-specific overexpression of the corresponding genes transcribed at an undetectable level during normal development and/or to an epithelial-mesenchymal transition proposed to occur during normal root formation. A plausible explanation for the results is that the odontogenic tumor epithelial cells are recapitulating genetic programs expressed during normal odontogenesis, but the tumor cells demonstrate abnormal expression patterns for these genes.

Clinical and Radiological Profile of Ameloblastic Fibro-Odontoma: an Update on an Uncommon Odontogenic Tumor Based on a Critical Analysis of 114 Cases

“…Only a small number of AFOs have been submitted to molecular and genetic studies but no significant findings have been found thus far that can contribute to our knowledge of the biological behavior of this lesion [96,97].…”

Selective but Nonspecific Immunolabeling of Enamel Protein-associated Compartments by a Monoclonal Antibody Against Vimentin

“…Vimentin has been detected in various mesenchymal cells types of the tooth organ, including odontoblasts (Lyn et al 1991;Seux et al 1991;Inoue et al 1992;Lombardi et al 1992a;Davidson 1994;Papagerakis et al 1999). The fact that we were unable to detect its presence in odontoblasts by high-resolution immunocytochemistry may be due to denaturation of antigenic sites during tissue processing and/or to its presence in amounts that are below the detectability threshold of Figure 1 Electron micrograph of rat incisor presecretory stage ameloblasts (PS-Am) at a position where they show short cytoplasmic processes (asterisks) extending into the forming mantle predentin.…”

Could wisdom tooth provide tooth germs for tooth regeneration?

“…In osteopetrotic (op/op) mice, incisor tooth germ could not erupt, but odontoma tissues are formed in the root apex instead due to the invasion of alveolar bone trabecular 9,10 . Owing to lack of some tooth eruption requirements, especially the osteoclastic induction factors 10 , one of the most intensively studied factors is macrophage colony-stimulating factor (M-CSF).…”