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

细胞表面的糖结合物与细胞的识别、生长和分化有关，而这些结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结合物进行了生化分析，并利用新建立的针对某一糖结合物的单抗建立了诊断子宫内膜癌的新方法。主要研究结果如下：1)人胎盘绒毛中主要的神经节苷脂IV^3NeuAcα-NLC_4Cer和II^3NeuAcLacCer(GM3)的浓度在妊娠过程中逐渐降低，提示这种特征性变化可能与胎盘绒毛的功能有关。硫脂是一种酸性糖脂，存在于正常子宫内膜组织中，且在正常分泌型子宫内膜中的含量高于增生期子宫内膜。分泌型子宫内膜中的Cerami…更多的中性糖脂的DES被羟化。在子宫内膜癌细胞中也检测到硫脂，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神经酰胺。在月经周期的不同阶段，子宫颈腺中糖脂的组成与子宫内膜相似，但在输卵管中，硫脂和羟化神经酰胺在整个周期中表达均匀。这些分析表明，某些子宫内膜脂的行为受到激素环境和恶变的影响。我们建立了识别子宫内膜癌中Leb相关糖脂糖基的单抗MSN-1，并将其用于开发子宫内膜癌的新诊断方法。流式细胞仪分析和子宫内膜糖脂分析显示，MSN-1很少与正常子宫内膜细胞反应，但与约70%的子宫内膜癌标本呈反应。通过子宫内膜细胞-EIA，其中直接使用由Endocyte或Endosearch获得的子宫内膜细胞，也注意到类似的结果。这些检测与恶变相关的糖结合改变的方法被认为有助于子宫内膜癌与正常子宫内膜的鉴别。CA54/61是本实验室确定的与CA72-4和唾液酸TN(STN)一样的粘蛋白型糖链相关抗原，是卵巢癌新的肿瘤标志物。免疫组织化学方法比较A54/61、CA72-4和STN的定位，结果表明这三种抗原不是SAIN抗原，而是密切相关的抗原。此外，他们的血清水平也很相似。较少

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