The purpose of this study was to assess the expression levels for TRI, TRII, and TRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TRs in carcinogenesis of oral mucosa.

Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches.

IHC signals for TRII and TRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TRI, in OLK and OSCC (P > 0.05); and TRII and TRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-1 led to a remarkable decrease in the expression of TRII and TRIII in CAFs (P < 0.05).

This study provides the first evidence that the loss of TRII and TRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TRII and TRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.

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