OBJECTIVE: The aim of this study was to determine the correlation between the number of FOXP3 + T cell in lesions and the disease activity of patients with oral lichen planus (OLP). MATERIALS AND METHODS: The expression of FOXP3 was investigated using immunohistochemical staining and real-time RT-PCR in 23 OLP lesions and 12 controls. Changes of FOXP3 + Treg in peripheral blood from three patients' pre and post-treatment were assessed using flow cytometry. RESULTS: Few FOXP3 + cells were detected in controls, but an increased number of FOXP3 + cells were observed in lesions (n = 20, 40.99 ± 24.68 cells per high-power field -hpf). Furthermore, the frequency of FOXP3 + Treg in reticular OLP (n = 7, 63.6 ± 23.2 cells per hpf) was significantly higher than that in erythematous ⁄ erosive OLP (n = 13, 28.8 ± 16.8 cells per hpf, P = 0.001). In addition, negative correlation was found between the number of FOXP3 + Treg and disease activity (correlation oefficient = )0.557, P = 0.013). The proportion of FOXP3 + Treg showed remarkable increase in peripheral blood from patients after treatment (1.39 ± 0.71% vs 4.91 ± 1.59%). CONCLUSIONS: These data indicated that FOXP3 + Treg were involved in the pathogenesis of OLP and correlated with disease's subtype and activity. Oral Diseases (2010) 16, 76-82

Oral carcinogenesis is a multistep process and requires accumulation and interplay of a series of molecular events. Chemokines and their receptors have been suggested to play important roles in the initiation or progression of cancers. Until now, no report focuses on their alterations in premalignant stage of oral squamous cell carcinoma (OSCC). Compared with normal tissues, mRNA levels of 9 chemokines and 3 chemokine receptors including CXCR7 in oral leukoplakia (OLK) were increased more than two folds by microarray analysis. Then, CXCR7 was selected for further confirmation and immunohistochemistry examination during multistage oral carcinogenesis. CXCR7 was expressed in 85% of OLK and 86% of OSCC. However, only 8% (1 of 13 cases) of normal tissue displayed CXCR7 immunostaining. The positive ratios of CXCR7, CXCL12 and CXCL11 in OLK and OSCC tissues respectively, were significantly higher than that in normal epithelia (P < 0.05), although no significant difference was found between OLK and OSCC. Meanwhile, CXCR7 always concomitantly expressed with it ligands in OLK and OSCC tissues. Our results indicated that CXCR7-CXCL12/CXCL11 axis might play important roles in oral carcinogenesis.

Objective: All-trans retinoic acid (ATRA) has been demonstrated to inhibit tumor growth by restoration of gap junctional intercellular communication (GJIC) via upregulation of connexin (Cx) expression in some solid tumors. However, the relationship between ATRA and GJIC remains unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the effect of ATRA on the GJIC function of OSCC. Study design: We measured the effects of ATRA on the viability and cell cycle distribution of SCC9 and Tca8113 OSCC cells. The GJIC function was observed using the scrape-loading dye transfer technique, and the mRNA and protein levels of Cx32 and Cx43 were detected by qRT-PCR, Western blot, and immunofluorescence assays. Results: ATRA inhibited the growth of OSCC cells in a dose- and time-dependent manner (P <0.05) and caused cell cycle arrest. ATRA-treated cells showed a 2.69-fold and 2.06-fold enhancement of GJIC in SCC9 and Tca8113 cells, respectively (P <0.05). Moreover, ATRA induced upregulation of Cx32 and Cx43 at both the mRNA and protein levels in OSCC cells. Conclusion: Our results indicated that restoration of GJIC via enhanced Cx32 and Cx43 expression might serve as a novel mechanism for the anti-tumor effect of ATRA in OSCC. Key words:All-trans retinoic acid, oral squamous cell carcinoma, connexin, gap junctional intercellular communication.

Oral carcinogenesis is a multistep process and requires accumulation and interplay of a series of molecular genetic events. Gap junctions are intercellular channels composed of connexin subunits that mediate cell-cell communication. The disfunctions of gap junctions are believed to be associated with cancer development. We therefore investigated the expression of connexin (Cx)43, one of the major connexins in oral epithelia, during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis. By immunohistochemistry, Cx43 expression was observed mainly in the cell membrane in normal rat oral epithelia. It was weak in the basal cell layer, increased in the stratum spinosum and stratum granulosum, and negative in the stratum corneum of normal epithelia. Throughout the course of carcinogenesis, both Cx43 immunostained area and mean intensity decreased with significant difference among various histopathological groups (P < 0.05). In cancerous oral epithelia cytoplasmic staining could be observed. However, Cx43 mRNA level showed no significant difference in the progress of oral carcinogenesis (P > 0.05) and without correlation to Cx43 protein immunostained area and mean intensity. Our results indicated that downregulation of Cx43 might be an early event during oral carcinogenesis, which could be a biomarker for early changes in oral malignant transformation.

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