Human beta-defensin-3 (hBD-3) upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance lymphatic invasion of oral squamous cell carcinoma

Objective. In this study, the hypothesis that hBD-3 is upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance metastasis in oral squamous cell carcinoma (OSCC) was tested. Study design. hBD-3 expression in human tissue specimens was evaluated by RT-qPCR and immunohistochemical staining. The presence of hBD-3 peptide in the culture supernatants of each type of treated cells was evaluated by enzyme-linked immunosorbent assay. The chemotaxis response to LPS or hBD-3 protein of SCC-25 cells or siRNA-hBD-3 transfected cells were also measured by chemotaxis assay. Paired, 2-tailed Student t test and analysis of variance was used to assess the statistical significance between 2 groups or many groups. Results. hBD-3 is highly expressed and associated with lymphatic invasion of OSCC. hBD-3 expression and EGFR phosphorylation were markedly upregulated when SCC-25 cells were treated with LPS. When SCC-25 cells were preincubated with EGFR inhibitor or TLR4-neutralizing Ab before LPS stimulation, a decrease in the expression of hBD-3 was observed. hBD-3 markedly enhanced cancer metastasis, and the chemotaxis response to LPS of SCC-25 cells was partly blocked by siRNA target hBD-3. Conclusion. These findings indicate that hBD-3 is upregulated by LPS via EGFR signaling pathways to enhance lymphatic invasion of OSCC. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112: 616-625)