期刊
BIOCHIMIE
卷 92, 期 7, 页码 852-857出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2010.02.012
关键词
Lewis Y; Integrin alpha 5 beta 1; Ovarian carcinoma; Adhesive; Spreading
资金
- National Natural Science Foundation of China [30170980, 30571958, 30872757]
- Liaoning Province Doctor Startup Fund [001040]
- Educational Department Science Foundation of Liaoning Province [05L492]
- Liaoning Natural Science Foundation [20052107]
- Educational Department Doctor Projects Fund [20070159023]
- Liaoning Province Education Office [2008S247]
- Shengjing Hospital [200807]
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 alpha 1,2-fucosyltransferase and compared their cellular properties with those of the original cells. So the human alpha 1,2-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 alpha 5 beta 1 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 alpha 5 beta 1, 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 alpha 1,2-fucosyltransferase gene into ovarian carcinoma-derived cells brought about elevated expression of integrin alpha 5 beta 1 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 alpha 5 beta 1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas. (C) 2010 Elsevier Masson SAS. All rights reserved.
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