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上皮性卵巢癌中Lewis y(Ley)血型抗原表达的血清学和免疫化学分析

Serological and immunochemical analysis of Lewis y (Ley) blood group antigen expression in epithelial ovarian cancer.

作者信息

Yin B W, Finstad C L, Kitamura K, Federici M G, Welshinger M, Kudryashov V, Hoskins W J, Welt S, Lloyd K O

机构信息

Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, USA.

出版信息

Int J Cancer. 1996 Feb 8;65(4):406-12. doi: 10.1002/(SICI)1097-0215(19960208)65:4<406::AID-IJC2>3.0.CO;2-0.

DOI:10.1002/(SICI)1097-0215(19960208)65:4<406::AID-IJC2>3.0.CO;2-0
PMID:8621218
Abstract

The expression of Ley blood group antigen in epithelial ovarian cancer tissues and cell lines has been studied using a Ley-specific monoclonal antibody (MAb 3S193). In ovarian cancer specimens, Ley was expressed in 75% of the 140 tumor specimens examined, with strong or moderate expression being observed in 56% of the samples. Seven of the 11 ovarian cancer cell lines studied were Ley-positive. Using immunochemical approaches, Ley epitopes were found to be expressed on 4 types of carrier molecules: CA125 ovarian cancer antigen, MUC-1 mucins, lower m.w. glycoproteins and glycolipids. In cell lines, Ley was more commonly expressed on MUC-1 mucin than on CA125, whereas in tumor specimens Ley was commonly found on both CA125 and MUC-1. The biochemical nature of the smaller Ley glycoproteins was not determined, but it was shown that they were not CEA and LAMP-1, known Ley carriers in some other tumor types. Glycolipids carrying Ley epitopes were detected in both ovarian cancer cell lines and tumor specimens. The presence of Ley epitopes on a number of different molecular carriers, including 2 major ovarian cancer antigens (CA125 and MUC-1), explains the high incidence of Ley in ovarian cancer. The high expression of Ley in ovarian cancer and the availability of specific murine and humanized MAbs make Ley an attractive candidate target for clinical studies.

摘要

利用一种抗Ley血型抗原的特异性单克隆抗体(MAb 3S193),对上皮性卵巢癌组织和细胞系中Ley血型抗原的表达情况进行了研究。在卵巢癌标本中,140例被检测的肿瘤标本中有75%表达Ley,其中56%的样本呈现强表达或中度表达。所研究的11种卵巢癌细胞系中有7种Ley呈阳性。采用免疫化学方法发现,Ley表位表达于4种载体分子上:CA125卵巢癌抗原、MUC-1黏蛋白、低分子量糖蛋白和糖脂。在细胞系中,Ley在MUC-1黏蛋白上的表达比在CA125上更常见,而在肿瘤标本中,Ley在CA125和MUC-1上均常见。较小的Ley糖蛋白的生化性质尚未确定,但已表明它们不是癌胚抗原(CEA)和溶酶体相关膜蛋白1(LAMP-1),而在其他一些肿瘤类型中,CEA和LAMP-1是已知的Ley载体。在卵巢癌细胞系和肿瘤标本中均检测到携带Ley表位的糖脂。Ley表位存在于多种不同的分子载体上,包括两种主要的卵巢癌抗原(CA125和MUC-1),这解释了Ley在卵巢癌中高表达的原因。Ley在卵巢癌中的高表达以及特异性鼠源和人源化单克隆抗体的可得性,使得Ley成为临床研究中一个有吸引力的候选靶点。

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