Abstract:
Oral cancer is one of the top 10 leading causes of death from cancer in Taiwan. This disease is characterized by poor prognosis and low survival rate. The molecular mechanisms of oral cancer progression are not well understood. Overexpression of L1 cell adhesion molecular (L1-CAM) has been found in many human carcinomas and is associated with tumor progression and poor prognosis. The aim of this study is to investigate the relationship between L1-CAM expression and tumor progression in tongue squamous cell carcinoma (TSCC) with a hope of understanding the molecular mechanisms of TSCC. The expression of L1-CAM in TSCC cell lines was determined by Western blotting, FACS, and ELISA analyses. Genetically manipulated TSCC stable cell lines with either over-expressed or down-regulated L1-CAM were generated by retroviral vector carrying L1-CAM cDNA transfection or lentiviral vector-mediated L1-CAM siRNA delivery, respectively. The resultant cell lines were determined and compared behavior changes including growth rate, migration and invasion in vitro using MTS and Transwell migration assay. We found that L1-CAM was detected in all testing TSCC cell lines (SAS, SCC4, SCC9, SCC25) with a variable expression level and negligible in human normal oral fibroblast cells. Over-expressed L1-CAM in L1-CAM low-expressing SCC25 cells enhanced cell growth, migration, invasion and attachment on fibronectin. Conversely, knockdown L1-CAM in L1-CAM highly-expressing SCC4 cells resulted in decreased cell ability in adhesion and motility. Moreover, L1-CAM mediated cell motility was in accordance with increased E-cadherin and decreased Vimentin and Fibronectin expression, suggesting that L1-CAM is involved in epithelial-mesenchymal transition (EMT) of TSCC. Our results demonstrated the first time that L1-CAM conferred TSCC tumor progression through the pathway of EMT. These findings also suggested that L1-CAM is a promising molecular target for the treatment of oral cancer.
