Possible involvement of ΔNp63 in invasion and metastasis of OSCC

Objectives: The present study was addressed to reveal the possible involvement of epithelial-mesenchymal transition (EMT) mediated by ΔNp63 in the invasion and metastasis in oral squamous cell carcinoma (OSCC). Patients and methods: A total of 60 patients with OSCC was analyzed by immunohistochemical double staining for ΔNp63 and vimentin. These labeling indices (LIs) at the invasive front in the tumor cells were calculated, and the association of these LIs with clinicopathologic characteristics in the OSCC was then evaluated. As well as ΔNp63, the expression of epithelial and mesenchymal markers was examined using RT-PCR and western blot methods in the OSCC cell lines. Furthermore, the effects of ΔNp63 siRNA transfection on the proliferation, differentiation and migration of the OSCC cells were examined. Results: Immunohistochemical double staining revealed that ΔNp63 was strongly and vimentin was not expressed in the tumor cells of superficial layer, but ΔNp63 was weakly and vimentin was strongly expressed at the invasive front. Furthermore, the frequencies of cervical lymph node and distant metastasis in the high vimentin-LI group (5%≤) were higher than these in the low LI group (5%>). Most of OSCC cell lines (HSC-2, HSC-3, SQUU-A, and SAS) expressed ΔNp63 and epithelial markers including cytokeratin (CK) 5 and 14, but vimentin was not expressed. However, in the OSCC cell line with high metastatic potential (SQUU-B), the expression of ΔNp63 and these epithelial markers was not detected, but increased expression of vimentin was found. By the transfection of ΔNp63 siRNA, the expression of epithelial markers was down-regulated and the expression of mesencymal markers including vimentin and N-cadherin was up-regulated in the HSC-2 cells. Furthermore, ΔNp63 knock down induced alteration of cellular morphorogy into fibroblastic cells, decreasing proliferation activity, and acquisition of high migratory capacity. Conclusion: Down-regulation of ΔNp63 induced acquisition of EMT cell phenotype and involved in the invasion and metastasis of OSCC cells.