| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Hiroaki Tokushima University, Graduate School of Health Bio Sciences, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 講師 (00243717)
MOMOTA Yukihiro Tokushima University, Graduate School of Health Bio Sciences, Assistant, 大学院・ヘルスバイオサイエンス研究部, 助手 (00304543)
HIGASHIKAWA Koichiro Hiroshima University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (80363084)
ONO Shigehiro Hiroshima University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (70379882)
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| Research Abstract |
In this research, we found that the SCCs of Yamamoto-Kohama 4D type, highly invasive SCCs, are the cells which acquired the epithelial-mesenchymal transition (EMT). Using the SCC cells with the EMT type, with epithelial morphologies, and EMT-induced SCC cells by transfection with Snail, we found that the EMT induced the loss of E-cadherin, epithelial morphology, and the gain of mesenchymal markers, highly invasive ability, and increased expression of Wnt-5a and MMP-2. The mechanism of the MMP-2 induction was associated with Ets-1, a newly identified EMT-target gene.
We established immortalized oral keratinocytes and gingival fibroblasts by gene transfer of hTERT. Using these cells, we established a three-dimensional culture. In this culture, the immortalized oral keratinocytes gained the invasive ability by MT1-MMP expression. The invasion was enhanced by co-expression of MMP-2. Furthermore, the SCC cells changed their modes of invasion by MT1-MMP expression. The invasion was further enhanced by expression of MMP-2 in the gingival fibroblasts.
Next, we identified EMT-associated genes using microarray and p63 revealed to be an EMT-target gene. Altered expression of p63 changed the morphology, invasion, and the expression of p63-down stream genes in SCC cells.
We studied the genes differently expressed in the SCC with or without metastasis. We found that CENP-F, a cell cycle associate gene, was a marker for the metastasis of SCC. Furthermore, we analyzed the expression profiling study of genes in the cell lines derived from the primary lesion and lymph node metastasis of a SCC arising in the tongue. We identified the some of the genes are common with the EMT-associated genes. Using other cancer but SCC, mainly gastric cancer, we studied the gene expression and their control mechanism with DNA methylation.
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