Analysis of glycoconjugates of the female genital tract : -with special reference to their changed dependent on the hormonal environment and malignant transformation-

女性生殖道糖缀合物的分析：-特别参考它们的变化依赖于激素环境和恶性转化-

• 批准号: 02454389
• 负责人: NOZAWA Shiro
• 金额: $ 4.42万
• 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: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454389/
• 关键词: glycoconjugate; female genital tract; glycolipid; sulfatide; ceramide; monoclonal antibody MSN-1; CA54; 61; 胎盤; 子宮体内膜; ハイドロキシ脂脂酸; シアリルパラグロボシド

Cell surface glycoconjugates are related to recognition, growth, and differentiation of cells, and changes in sugar cliains of these conjugates have been associated with malignant transformation. We analyzed biochemically the glycoconjugates in various organs of the female genital tract, and also developed new diagnostic methods for endometrial cancer by using a newly established monoclonal antibody directed against a certain glycoconjugate. The following results were obtained from our studies :1.) The concentration of IV ^3NeuAc alpha-nLc_4Cer, a major ganglioside along with II ^3NeuAcLacCer (GM3) in human placental villi, was found to decrease gradually there during gestation, suggesting that this characteristic alteration might be related to the function of the villi.2.) Sulfatide, one of tlie acidic glycolipids, was found in normal endometrial tissue, and its amount was larger in normal secretory endometrium than in the proliferative-phase type. In secretory endometrium, the cerami … More des of neutral glycolipids were shown to be hydroxylated. Sulfatide was also detected in endoinetrial cancer cells, and long-chain sugars and hydroxylated ceramides of neutral glycolipids were also found in well-differentiated endometrial cancers. In the cervical glands the composition of glycolipids was similar to that in the endometrium at the different phases of the menstrual cycle, but in the fallopian tubes sulfatide and hydroxylated ceramides were expressed uniformly throughout the cycle. These analyses revealed that the behavior of some endometrial glicolipids was influenced by the hormonal environment and by malignant transformation.3.) We established MSN-1, monoclonal antibody that recognizes a Leb-related sugar moiety of glycolipids in endometrial cancer, and used it to develop new diagnostic methods for endometria cancer. Flow cytometric analysis and Endometrial Glycolipid Assay revealed that MSN-1 seldom reacted with normal endometrial cells but that it was reactive with about 70% of endometrial cancer specimens. By Endometrial Cell-EIA, in which endometrial cells obtained by Endocyte or Endosearch were used directly, similar results were noted. These methods detecting glycoconjugate changes associated with malignant transformation were considered useful in differentiating endometrial cancer from normal endometrium.4.) CA54/61, determined in our laboratory to be a mucin-type sugar chain-related antigen like CA72-4 and sialil Tn (STN), was established as a novel tumor marker of ovarian cancer. The localization of A54/61 was compared with that of CA72-4 and STN immunohistochemically, and the results indicated that these three antigens were not the saine ones but were closely related. Also, their serum levels resembled each other. Less

细胞表面糖缀合物与细胞的识别、生长和分化有关，这些缀合物糖链的变化与恶性转化有关。我们对女性生殖道各器官中的糖缀合物进行了生化分析，并通过使用新建立的针对某种糖缀合物的单克隆抗体开发了子宫内膜癌的新诊断方法。我们的研究取得了以下结果：1）。人胎盘绒毛中主要神经节苷脂IV ^3 NeuAc α-nLc_4 Cer（沿着II ^3 NeuAcLacCer（GM 3））的浓度在妊娠期间逐渐降低，这表明这种特征性变化可能与绒毛的功能有关。硫酸脂是一种酸性糖脂，存在于正常子宫内膜组织中，其含量在正常分泌期子宫内膜高于增殖期子宫内膜。在分泌期子宫内膜中， ...更多信息 中性糖脂的DES显示为羟基化的。在子宫内膜癌细胞中也检测到硫苷脂，在分化良好的子宫内膜癌中也发现了长链糖和中性糖脂的羟基化神经酰胺。在宫颈腺体中，糖脂的组成与月经周期不同阶段子宫内膜中的糖脂组成相似，但在输卵管中，硫苷脂和羟基化神经酰胺在整个周期中均匀表达。这些分析表明，一些子宫内膜糖脂的行为受到激素环境和恶性转化的影响。我们建立了MSN-1，单克隆抗体，识别子宫内膜癌中糖脂的Leb相关糖部分，并使用它来开发子宫内膜癌的新诊断方法。流式细胞术分析和子宫内膜糖脂测定显示MSN-1很少与正常子宫内膜细胞反应，但它与约70%的子宫内膜癌标本反应。通过Endocyte或Endosearch获得的子宫内膜细胞直接使用的子宫内膜细胞EIA，观察到类似的结果。这些检测与恶性转化相关的糖缀合物变化的方法被认为是有用的，以区分子宫内膜癌和正常子宫内膜。CA 54/61与CA 72 -4和唾液酸Tn（sialil Tn）一样，是一种粘蛋白型糖链相关抗原，被本实验室确定为一种新的卵巢癌肿瘤标志物。将A54/61与CA 72 -4和IgM进行了化学定位比较，结果表明这三种抗原不是同一抗原，但有密切的关系。此外，他们的血清水平彼此相似。少

项目成果

野澤 志朗: "子宮内膜と胎盤の糖脂質分析" 産婦人科の世界. 43(1). 31-38 (1991)

Shiro Nozawa：“子宫内膜和胎盘的糖脂分析”《妇产科世界》43（1）31-38（1991）。

Mikio Mikami, et al: "Menstrual cycle-associated expression of 2-hydroxy matty acyl Phytosphingosine-containing GlcCer, LacCer and Gb_<3->Cer in human uterine endometrium." Bioch Biophys Acta.

Mikio Mikami 等人：“人子宫内膜中含有 2-羟基马蒂酰基植物鞘氨醇的 GlcCer、LacCer 和 Gb_3->Cer 与月经周期相关的表达。”

Kaneyuki Kubushiro, et al: "Human uterine endometrial adenocarcinoma-characteristic acquirement of synthetic potential for II ^3So_3-LacCer and Gangrio-series Sulfo-glycosphingolipids after transfer the cancer to cultivation." Cancer Res.

Kaneyuki Kubushiro 等人：“人类子宫内膜腺癌 - 将癌症转移到培养物后获得 II ^3So_3-LacCer 和 Gangrio 系列磺基鞘糖脂的合成潜力的特征。”

Katsumi Tsukazaki: "Abnormal expression of blood groupーrelated antigens in uterine endometrial cancers" Japanese Journal of Cancer Research. 82(8). 934-941 (1991)

Katsumi Tsukazaki：“子宫内膜癌中血型相关抗原的异常表达”日本癌症研究杂志 82(8) 934-941 (1991)。

Kaneyuki Kubushiro: "Human uterine endometrial adenocarcinomaーcharacteristic acqirment of synthetic potential for II^3SO_3ーLacCer and Ganglioーseries Sulfoーglycosphingolipids after transfer the cancer to cultivation" Cancer Research.

Kaneyuki Kubushiro：“人类子宫内膜腺癌-将癌症转移到培养物后获得 II^3SO_3-LacCer 和神经节系列磺基鞘糖脂的合成潜力的特征”癌症研究。