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Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China
Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan
* Author to whom correspondence should be addressed.
Received: 25 October 2010; in revised form: 30 October 2010 / Accepted: 31 October 2010 / Published: 8 November 2010
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.
Keywords: Lewis (y) antigen; matrix metalloproteinases; tissue inhibitors of metalloproteinases; invasion
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Yan, L.; Lin, B.; Gao, L.; Gao, S.; Liu, C.; Wang, C.; Wang, Y.; Zhang, S.; Iwamori, M. Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells. Int. J. Mol. Sci. 2010, 11, 4441-4451.
Yan L, Lin B, Gao L, Gao S, Liu C, Wang C, Wang Y, Zhang S, Iwamori M. Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells. International Journal of Molecular Sciences. 2010; 11(11):4441-4451.
Yan, Limei; Lin, Bei; Gao, Lili; Gao, Song; Liu, Chuan; Wang, Changzhi; Wang, Yifei; Zhang, Shulan; Iwamori, Masao. 2010. "Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells." Int. J. Mol. Sci. 11, no. 11: 4441-4451.