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刘易斯 Y 通过上调生长因子促进卵巢癌细胞衍生的 RMG-I 细胞的生长和黏附。

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

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 36 Sanhao Street, Heping, Shenyang, 110004, China; E-Mails:

出版信息

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.

摘要

Lewis y(LeY)抗原是一种在细胞表面糖缀合物上携带的双岩藻糖基化寡糖。LeY 的过表达在上皮源性癌中经常观察到,并与病理分期和预后相关。然而,LeY 对卵巢癌的影响尚不清楚。以前,我们通过转染 α1,2-岩藻糖基转移酶基因使卵巢癌细胞系 RMG-I 获得稳定转染系 RMG-I-H,该细胞系高表达 LeY。在本研究中,我们用 LeY 单克隆抗体(mAb)处理这些细胞系,检测它们的增殖、致瘤性、黏附和侵袭能力。此外,我们还检测了异种移植瘤中 TGF-β1、VEGF 和 b-FGF 的表达。结果表明,LeY mAb 处理 RMG-I-H 细胞可显著抑制其体外增殖和黏附。当皮下接种于裸鼠时,RMG-I-H 细胞产生大肿瘤,而 mock 转染的 RMG-I-C 细胞和亲本细胞 RMG-I 产生小肿瘤。此外,LeY mAb 预先孵育 RMG-I-H 细胞可抑制肿瘤形成。值得注意的是,RMG-I-H 细胞中 TGF-β1、VEGF 和 b-FGF 的表达均增加。总之,LeY 在促进细胞增殖、致瘤性和黏附方面发挥重要作用,这些作用可能与生长因子水平的升高有关。LeY 抗体在治疗 LeY 阳性肿瘤方面具有潜在的应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4cf/2996800/1bada76a8b85/ijms-11-03748f1.jpg

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