Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin α5β1 with the Lewis Y-structure on transfection of the α1,2-fucosyltransferase gene

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• 作者：Li-Mei Yan ; Bei Lin ; Lian-Cheng Zhu ; Ying-Ying Hao ; Yue Qi ; Chang-Zhi Wang ; Song Gao ; Shui-Ce Liu ; Shu-Lan Zhang ; Masao Iwamori
• 关键词：Lewis Y ; Integrin α ; 5β ; 1 ; Ovarian carcinoma ; Adhesive ; Spreading
• 刊名：Biochimie
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：92
• 期：7
• 页码：852-857
• 全文大小：1054 K

文摘

Le^Y antigen is known to be associated with malignant properties including metastasis and a poor prognosis of ovarian carcinomas. To clarify the mechanisms underling these properties, we established ovarian carcinoma-derived cells exhibiting enhanced expression of Le^Y by transfection with α1,2-fucosyltransferase and compared their cellular properties with those of the original cells. So the human α1,2-fucosyltransferase gene was transfected into ovarian carcinoma-derived RMG-1 cells, which are known to contain Le^X, a precursor of Le^Y, and RMG-1-hFUT cells exhibiting enhanced expression of Le^Y were established by selection with anti-Le^Y antibodies, and their adhesive and spreading potentials on fibronectin-coated plates were compared with those of RMG-1 cells. Results showed that the relative expression of Le^Y in RMG-1-hFUT cells was about 20-fold that in RMG-1 cells, and that of integrin α5β1 and an integrin-mediated signal transduction molecule, focal adhesion kinase, was also increased in RMG-1-hFUT cells. Interestingly, anti-Le^Y antibodies were revealed to immunoprecipitate integrin α5β1, indicating that its oligosaccharides are composed of Le^Y, the amounts of which was substantially elevated in RMG-1-hFUT cells. The adhesion and spreading potentials on fibronectin-coated plates of RMG-1-hFUT cells were significantly enhanced in comparison to those of RMG-1 cells, and were greatly suppressed by anti-Le^Y antibodies, indicating that Le^Y is involved in the integrin–fibronectin interaction. These results suggested that transfection of the α1,2-fucosyltransferase gene into ovarian carcinoma-derived cells brought about elevated expression of integrin α5β1 with Le^Y, resulting in enhancement of the adhesion and spreading potentials of cells through the integrin–fibronection interaction, which was inhibited by anti-Le^Y antibodies. Thus, Le^Y in integrin α5β1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas.