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

细胞表面糖缀合物与细胞的识别、生长和分化有关，这些缀合物的糖偶联物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，并利用新建立的针对特定糖缀合物的单克隆抗体，开发了新的子宫内膜癌诊断方法。从我们的研究中得到以下结果：1.)IV ^3NeuAc α - nlc_4cer与II ^3NeuAcLacCer （GM3）是人类胎盘绒毛中的一种主要神经节苷脂，在妊娠期间，IV ^3NeuAc α - nlc_4cer的浓度逐渐下降，这表明这种特征的改变可能与绒毛的功能有关。硫脂是一种酸性糖脂，在正常子宫内膜组织中发现，其量在正常分泌型子宫内膜中比在增殖期型子宫内膜中要大。在分泌性子宫内膜中，中性糖脂被羟基化。在子宫内膜癌细胞中也发现了硫脂，在分化良好的子宫内膜癌中也发现了中性糖脂的长链糖和羟基化神经酰胺。在月经周期的不同阶段，宫颈腺中糖脂的组成与子宫内膜相似，但在输卵管中，硫脂和羟基化神经酰胺在整个月经周期中均匀表达。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。我们建立了识别子宫内膜癌糖脂中leb相关糖片段的单克隆抗体MSN-1，并将其用于子宫内膜癌的诊断。流式细胞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发生反应，但与约70%的子宫内膜癌标本发生反应。直接使用Endocyte或Endosearch获得的子宫内膜细胞进行子宫内膜细胞eia试验，结果相似。这些检测与恶性转化相关的糖结合物变化的方法被认为是鉴别子宫内膜癌与正常子宫内膜的有用方法。我们实验室确定CA54/61与CA72-4、sialil Tn （STN）一样是粘蛋白型糖链相关抗原，建立了新的卵巢癌肿瘤标志物。用免疫组化方法将A54/61抗原与CA72-4、STN抗原定位进行比较，结果表明这三种抗原不是同一种抗原，而是密切相关的。而且，他们的血清水平相似。少

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