Lewis Y promotes growth and adhesion of ovarian carcinoma-derived RMG-I cells by upregulating growth factors

Int J Mol Sci. 2010 Sep 29;11(10):3748-59. doi: 10.3390/ijms11103748.

Abstract

Lewis y (LeY) antigen is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Overexpression of LeY is frequently observed in epithelial-derived cancers and has been correlated to the pathological staging and prognosis. However, the effects of LeY on ovarian cancer are not yet clear. Previously, we transfected the ovarian cancer cell line RMG-I with the α1,2-fucosyltransferase gene to obtain stable transfectants, RMG-I-H, that highly express LeY. In the present study, we examined the proliferation, tumorigenesis, adhesion and invasion of the cell lines with treatment of LeY monoclonal antibody (mAb). Additionally, we examined the expression of TGF-β1, VEGF and b-FGF in xenograft tumors. The results showed that the proliferation and adhesion in vitro were significantly inhibited by treatment of RMG-I-H cells with LeY mAb. When subcutaneously inoculated in nude mice, RMG-I-H cells produced large tumors, while mock-transfected cells RMG-I-C and the parental cells RMG-I produced small tumors. Moreover, the tumor formation by RMG-I-H cells was inhibited by preincubating the cells with LeY mAb. Notably, the expression of TGF-β1, VEGF and b-FGF all increased in RMG-I-H cells. In conclusion, LeY plays an important role in promoting cell proliferation, tumorigenecity and adhesion, and these effects may be related to increased levels of growth factors. The LeY antibody shows potential application in the treatment of LeY-positive tumors.

Keywords: Lewis y; adhesion; inhibition; ovarian cancer; proliferation; tumorigenecity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis*
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Lewis Blood Group Antigens / genetics
  • Lewis Blood Group Antigens / metabolism*
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Lewis Blood Group Antigens
  • Lewis Y antigen
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factors