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

LeY 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 LeY 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 LeX, a precursor of LeY, and RMG-1-hFUT cells exhibiting enhanced expression of LeY were established by selection with anti-LeY 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 LeY 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-LeY antibodies were revealed to immunoprecipitate integrin α5β1, indicating that its oligosaccharides are composed of LeY, 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-LeY antibodies, indicating that LeY 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 LeY, resulting in enhancement of the adhesion and spreading potentials of cells through the integrin–fibronection interaction, which was inhibited by anti-LeY antibodies. Thus, LeY in integrin α5β1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas.