Tenascin-C Expression in Relation to Tumor-Stroma Interaction in Ameloblastoma

Abstract

Ameloblastoma (AM) is a benign epithelial odontogenic tumor that occurs in the jawbone. Although benign, AM can exhibit aggressive features, including locally invasive growth. In addition, local recurrence or distant metastasis may occur. Therefore, understanding the mechanisms underlying AM-cell migration is essential for improving clinical therapy. The role of the tumor microenvironment in disease progression has been extensively studied in various tumors. In the microenvironment, it has been reported that the extracellular matrix plays many roles. Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is highly expressed during tissue development and remodeling. In this study, we investigated the involvement of TN-C in AM progression. Immunohistochemical analysis of AM specimens revealed high TN-C protein expression in the stroma, particularly at the invasive front. In contrast, RNA in situ hybridization demonstrated that TNC was localized within tumor cells, suggesting that the TN-C protein in the stroma is secreted by tumor cells rather than produced by stromal cells. In in vitro analyses, TN-C expression was significantly upregulated in cocultures of the AM cell line, AM-1, and primary human periodontal ligament fibroblasts, indicating that tumor-stroma interactions enhance tumor-derived TN-C expression. Functionally, TN-C stimulation promoted AM-cell migration, whereas TNC knockdown suppressed it. Spatial transcriptomics revealed elevated TNC expression in regions undergoing malignant transformation. Our results demonstrate that tumor-derived TN-C promotes AM progression. The expression of TN-C at the invasive front and in malignant regions suggests its potential as both a prognostic marker and a therapeutic target in tumor progression.