Zhuang Huiyu, Hu Zhenhua, Tan Mingzi, Zhu Liancheng, Liu Juanjuan, Liu Dawo, Yan Limei, Lin Bei
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004 Liaoning Province, China.
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004 Liaoning Province, China.
Biochimie. 2014 Oct;105:91-8. doi: 10.1016/j.biochi.2014.06.022. Epub 2014 Jul 4.
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.
为研究人附睾蛋白4（HE4）的表面岩藻糖基化，并确定Lewis y抗原对HE4介导的卵巢癌细胞侵袭和转移的影响及意义，我们研究了四种卵巢癌细胞系，发现卵巢癌细胞中的HE4上存在六种岩藻糖基化抗原（Lewis y、Lewis x、Lewis a、Lewis b、sLewis a和sLewis x）。此外，乳糖系列的II型糖链（Lewis y、Lewis x和sLewis x）的修饰明显高于I型糖链（Lewis a、Lewis b、sLewis a）。为证实Lewis y抗原对HE4介导的卵巢癌细胞侵袭和转移的影响，我们研究了HE4表面Lewis y抗原高表达的CaoV-3细胞系以及Lewis x抗原高表达但Lewis y抗原低表达的ES-2细胞系。我们发现，转染后两种细胞系中HE4和Lewis y的表达水平均升高，而Lewis x的水平没有变化。此外，Lewis y抗原的高表达显著增强了HE4介导的卵巢癌细胞侵袭和转移。Lewis y抗体阻断后，侵袭和转移能力显著降低。本研究表明，HE4上Lewis y抗原的过表达促进卵巢癌细胞侵袭和转移，有望作为卵巢癌临床治疗的靶点。
