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Analysis and Clinical Significance on the Carbohydrate Chain Gene related to the Peritoneal Dissemination of Ovarian Cancer.

卵巢癌腹膜播散相关糖链基因分析及临床意义。

基本信息

批准号：
11671659
负责人：
KIGUCHI Kazushige
金额：
$ 2.43万
依托单位：
St.Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Cells of the human tumor cell line RMG-1, derived from a clear-cell adenocarcinoma of the ovary, were injected intraperitoneally into nude mice, and the cells obtained from the tumor nodules in the mesenterium were found to form a larger number of, and larger-sized, tumor nodules than the original RMG-1 cells. The RMG-1-h cells, transferred into culture from the tumor nodules after a 4th in vivo passage, showed a dissemination potential as high as that of cells disseminating directly from the tissues, and exceedingly higher than that of RMG-1 cells. To assess the molecular bases of the different biological properties of RMG-1 and RMG-1-h cells, we compared the content and expression of various carbohydrate antigens in both cells. In contrast to the broad histogram for the Le^x-bearing cells among RMG-1 cells in flow cytometry, the weakly and moderately positive cells toward anti-Le^x antibody were found to be eliminated from the histogram for the RMG-1-h cells, resulting in the enrichment of cells strongly expressing Le^x, which may account for the high dissemination potential. In addition, the adhesion of RMG-1 cells to mesothelial cells was found to be significantly inhibited by pretreatment of the cells with anti-Le^x antibody, indicating Le^x-mediated cell-to-cell interaction between ovarian cancer cells and mesothelial cells. By TLC-immunostaining, two Le^x-glycolipids, III^3Fuc α-nLc_4Cer and V^3Fuc α-nLc_6Cer were detected in both RMG-1 and RMG-1-h cells, and the hydrophobic moieties of Le^x-glycolipids in RMG-1-h cells were different from those in RMG-1 cells. Thus, the high dissemination potential of ovarian cancer cells was shown to be mediated by the Le^x-determinant and the Le^x-bearing cells are enriched by repeated in vivo passage of the cells into nude mice.

将来源于卵巢透明细胞腺癌的人肿瘤细胞系RMG-1的细胞腹膜内注射到裸鼠中，发现从肠系膜中的肿瘤结节获得的细胞形成比原始RMG-1细胞更多且更大的肿瘤结节。在第4次体内传代后从肿瘤结节转移到培养物中的RMG-1-h细胞显示出与直接从组织播散的细胞一样高的播散潜力，并且远远高于RMG-1细胞。为了评估RMG-1和RMG-1-h细胞不同生物学特性的分子基础，我们比较了两种细胞中各种糖抗原的含量和表达。与流式细胞术中RMG-1细胞中携带Le^x的细胞的宽直方图相反，发现抗Le ^x抗体的弱阳性和中度阳性细胞从RMG-1-h细胞的直方图中消除，导致强表达Le^x的细胞富集，这可能是高传播潜力的原因。此外，发现用抗Le ^x抗体预处理细胞显著抑制RMG-1细胞与间皮细胞的粘附，表明卵巢癌细胞与间皮细胞之间存在Le^x介导的细胞间相互作用。TLC免疫组化结果显示，RMG-1和RMG-1-h细胞中均检测到两种Le^x糖脂，即Ⅲ ^3 Fuc α-nLc_4Cer和Ⅴ ^3 Fuc α-nLc_6Cer，且RMG-1-h细胞中Le^x糖脂的疏水部分与RMG-1细胞中的不同。因此，卵巢癌细胞的高扩散潜力被证明是由Le^x决定簇介导的，并且通过将细胞重复体内传代到裸鼠中来富集携带Le^x的细胞。