扁平上皮癌の高度浸潤能獲得過程におけるSnailの発現とその作用

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  • Expression and functions of Snail in acquiring high invasive ability in sequamous carcinoma cells

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Loss of cell-cell adhesion and degradation of extracellular matrix are necessary for infiltration and metastasis of cancer cells. E-cadherin is a calcium-dependent cell adhesion molecule and the loss of E-cadherin expression has been reported in highly invasive sequamous cell carcinomas (SCCs) . Recently, a transcription factor Snail was identified as repressor of E-cadherin. In this report, we found that HOC719, a cell line derived from oral SCC, expressed E-cadherin heterogeneously and we isolated E-cadherin positive (HOC719-PE) and negative cells (HOC719-NE) from this cell line. HOC719-PE cells showed epithelial cell shape, while HOC719-NE cells showed fibroblastic. Moreover, HOC719-NE cells had higher invasive ability and expressed MMP-2 and Snail mRNA more strongly than HOC719-PE cells. Then we studied the effects of Snail expression in E-cadherin positive cells by transfecting a Snail expression vector. E-cadherin promoter activity decreased in transiently Snail transfected A431 and HOC719 - PE cells. Stably Snail-expressing A431 cells changed to the fibroblastic morpbology and acquired more invasive ability. By the RT-PCR analysis, these Snail-expressing cells showed decreased expression of E-cadherin but increased expression of MMP-2. Furthermore, overexpressing of Snail induced the increased MMP-2 promoter activity of A431 and HOC719-PE cells by the luciferase reporter assay.<BR>These results indicate that Snail plays a key role in the acquisition of more invasive phenotypes of SCC via changing the cell shape and expression of E-cadherin and MMP-2.

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