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Analysis of Glycolipids in Human Endometrium - using mouse and human monoclonal antibodies -

人子宫内膜中的糖脂分析 - 使用小鼠和人单克隆抗体 -

基本信息

批准号：
62480351
负责人：
NOZAWA Shiro
金额：
$ 4.16万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Since glycolipids on the cell membrane act as a factor in cell recognition, their counterparts in the endometrium may play an important role in implantation. Because sugar chain of glycolipids have been shown to change after malignant transformation, glycolipids may serve as an important diagnostic marker of endometrial cancer. Therefore, we decided to analyze the composition of these molecules from normal and malignant endometric with the aim of developing a new diagnostic method for detection of endometrial cancers.We found that sulfatide, one of the acidic glycolipids, is present in normal endometrial cells and that its amount in the secretory phase is greater than that in the proliferative phase, suggesting that such glycolipid may be involved in implantation. Furthermore, we found that sulfotransferase activity, which is necessary for sulfatide synthesis, is present in endometrial cancer cells; which may indicate that sex steroid hormones have something to do with the gene expression of this enzyme.We developed two monoclonal antibodies against endometrial cancers. One of them, MSN-1, reacts with the Le^b-related sugar moiety of mouse glycolipid; and the other, HMST-1, reacts with human glycolipid type I sugar chain. We applied MSN-1 to flow cytometry to develop a diagnostic method for endometrial cancer, and found that this monoclonal seldom reacted with normal endometrial cells but was reactive with neoplastic cells in 70% of the endometrial cancer cases examined. Our data indicate that this method is very useful for the diagnosis of endometrial cancers.

由于细胞膜上的糖脂是细胞识别的一个因素，因此子宫内膜中的糖脂可能在植入过程中发挥重要作用。由于糖脂的糖链在恶变后会发生变化，因此糖脂可能作为子宫内膜癌的重要诊断标志物。因此，我们决定分析正常和恶性子宫内膜细胞中这些分子的组成，旨在开发一种检测子宫内膜癌的新诊断方法。我们发现正常子宫内膜细胞中存在酸性糖脂之一的硫苷脂，并且其在分泌期的含量高于增殖期，表明此类糖脂可能参与着床。此外，我们发现子宫内膜癌细胞中存在硫苷脂合成所必需的磺基转移酶活性；这可能表明性类固醇激素与这种酶的基因表达有关。我们开发了两种针对子宫内膜癌的单克隆抗体。其中之一，MSN-1，与小鼠糖脂的 Le^b 相关糖部分发生反应；另一个是HMST-1，与人糖脂I型糖链发生反应。我们将MSN-1应用于流式细胞术，开发了一种子宫内膜癌的诊断方法，发现这种单克隆抗体很少与正常子宫内膜细胞发生反应，但在70%的子宫内膜癌病例中与肿瘤细胞发生反应。我们的数据表明该方法对于子宫内膜癌的诊断非常有用。