Overexpression of Lewis y antigen promotes human epididymis protein 4-mediated invasion and metastasis of ovarian cancer cells.

Abstract

To study Human epididymis protein 4 (HE4) surface fucosylation and to determine the effects and significance of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, we investigated four types of ovarian cancer cells and found that six fucosylated antigens (Lewis y, Lewis x, Lewis a, Lewis b, sLewis a, and sLewis x) were identified on HE4 in ovarian cancer cells. Moreover, modification of the type II sugar chain (Lewis y, Lewis x, and sLewis x) was significantly higher than the type I sugar chain (Lewis a, Lewis b, sLewis a) of the lactose series. To confirm the effects of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, the CaoV-3 cells with high Lewis y antigen on the HE4 surface and ES-2 cells, with high Lewis x antigen but low Lewis y antigen, were investigated. We found that the expression levels of HE4 and Lewis y increased in both cell lines while the level of Lewis x didn't have any change after transfection. Furthermore, the high expression of Lewis y antigen significantly enhanced the HE4-mediated invasion and metastasis of ovarian cancer cells. The invasion and metastasis capacities were significantly decreased after Lewis y antibody blocking. This study demonstrates that overexpression of the Lewis y antigen on HE4 promotes ovarian cancer cell invasion and metastasis, which is likely to be used as a target for the clinical treatment of ovarian cancer.

• Authors: Huiyu Zhuang, Zhenhua Hu, Mingzi Tan, Liancheng Zhu, Juanjuan Liu, Dawo Liu, Limei Yan, Bei Lin
• Journal: Biochimie (Biochimie) Vol. 105 Pg. 91-8 (Oct 2014) ISSN: 1638-6183 [Electronic] France
• PMID: 24998328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Lewis Blood Group Antigens
• Lewis Y antigen
• Proteins
• WAP Four-Disulfide Core Domain Protein 2
• WFDC2 protein, human

Topics

• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lewis Blood Group Antigens (biosynthesis, metabolism)
• Neoplasm Invasiveness (genetics)
• Neoplasm Metastasis
• Ovarian Neoplasms (genetics, pathology)
• Proteins (genetics, metabolism)
• WAP Four-Disulfide Core Domain Protein 2