Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin alpha5beta1 with the Lewis Y-structure on transfection of the alpha1,2-fucosyltransferase gene.
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 alpha1,2-fucosyltransferase and compared their cellular properties with those of the original cells. So the human alpha1,2-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 alpha5beta1 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 alpha5beta1, 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 alpha1,2-fucosyltransferase gene into ovarian carcinoma-derived cells brought about elevated expression of integrin alpha5beta1 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 alpha5beta1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas.
Yan
Li-Mei
LM
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, PR China.
Lin
Bei
B
Zhu
Lian-Cheng
LC
Hao
Ying-Ying
YY
Qi
Yue
Y
Wang
Chang-Zhi
CZ
Gao
Song
S
Liu
Shui-Ce
SC
Zhang
Shu-Lan
SL
Iwamori
Masao
M
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048429:Cell Size; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000378:metabolism*; D007983:Lewis Blood Group Antigens / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D014162:Transfection
D005353:Fibronectins; D039081:Integrin alpha5beta1; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D005647:Fucosyltransferases; D051416:Focal Adhesion Protein-Tyrosine Kinases