Lewis (y) antigen overexpression increases the expression of MMP-2 and MMP-9 and invasion of human ovarian cancer cells.

Abstract

Lewis (y) antigen is a difucosylated oligosaccharide present on the plasma membrane, and its overexpression is frequently found in human cancers and has been shown to be associated with poor prognosis. Our previous studies have shown that Lewis (y) antigen plays a positive role in the process of invasion and metastasis of ovarian cancer cells. However, the mechanisms by which Lewis (y) antigen enhances the invasion and tumor metastasis are still unknown. In this study, we established a stable cell line constitutively expressing Lewis (y) antigen (RMG-1-hFUT) by transfecting the cDNA encoding part of the human α1,2-fucosyltransferase (α1,2-FUT) gene into the ovarian cancer cell line RMG-1, and investigated whether Lewis (y) antigen regulates the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and tissue inhibitors of metalloproteinases (TIMP-1) and TIMP-2. We found that RMG-1-hFUT cells exhibited higher invasive capacities than their control cells. In addition, expression of TIMP-1 and TIMP-2 was down-regulated and expression of MMP-2 and MMP-9 was up-regulated. Anti-Lewis (y) antigen antibody treatment significantly reversed the expression of TIMP-1, TIMP-2, MMP-2 and MMP-9. Taken together, we provide the first evidence that down-regulation of TIMP-1 and TIMP-2 and up-regulation of MMP-2 and MMP-9 represents one of the mechanisms by which Lewis (y) antigen promotes cell invasion.

• Authors: Limei Yan, Bei Lin, Lili Gao, Song Gao, Chuan Liu, Changzhi Wang, Yifei Wang, Shulan Zhang, Masao Iwamori
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 11 Issue 11 Pg. 4441-52 (Nov 08 2010) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 21151448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lewis Blood Group Antigens
• Lewis Y antigen
• TIMP1 protein, human
• TIMP2 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-2
• Fucosyltransferases
• galactoside 2-alpha-L-fucosyltransferase
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Cell Line, Tumor
• Female
• Fucosyltransferases (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Lewis Blood Group Antigens (genetics, metabolism)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Neoplasm Invasiveness
• Ovarian Neoplasms (metabolism, pathology)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)
• Tissue Inhibitor of Metalloproteinase-2 (genetics, metabolism)