An Investigation of the Mechanisms and Functions of L-selectin (SELL) Overexpression in Oral Cancer

• Main Authors: Chun-Fu Lin, 林俊甫
• Other Authors: Kuo-Wei Chang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/16155650889753280398

碩士 === 國立陽明大學 === 口腔生物研究所 === 97 === Oral squamous cell carcinoma (OSCC) is the fourth most prevalent malignancy in male of our country. L-selectin (SELL) belongs to cell adhesion molecules (CAM), and is one of the selectin family. SELL mainly expresses on the cell membrane of leukocytes, and regulates the rolling and attachment of leukocytes with endothelial cells. However, our previous study showed that the expression of SELL on cells from metastatic lesions were higher than those from primary OSCC. Furthermore, the patients who exhibiting higher SELL expression had lower survival rate than those with lower SELL expression. Therefore, SELL may play a pivotal role in the development of metastasis. Till far, the mechanisms of SELL in promoting neoplastic progression of solid tumor are still unclear. The aims of this study are to investigate the functions of SELL overexpression and the mechanisms regulating SELL expression in OSCC cells. We constructed the plasmid DNA containing SELL and GFP genes for several phenotypic analysis. The results showed that the SELL-overexpressed OSCC cells had higher abilities of migration, invasion and anchorage-independent growth comparing with control groups in vitro. The in vivo tumorigenic experiments showed significant difference in tumor growth between SELL-overexpressed SAS cells and control groups. We also constructed the plasmid DNA containing the promoter region of SELL gene. The reporter assay showed that the promoter activity of SELL was upregulated about 1.5 fold than control groups. Althogh the SELL-overexpressed SAS cells were assumed to have higher metastatic potential than control groups, the SELL overexpression did not upregulate MAPK, FAK, Akt, apoptosis related (Bcl-2 and caspase-3) or epithelial-mesenchymal transition (EMT) related (fibronectin and E-cadherin) pathways in OSCC cells. However, vimentin and cytokeratin were downregulated in SELL-overexpressed SAS cells. Therefore, SELL overexpression may increase the oncogenic potential in OSCC cells by disrupting cytoskeleton.