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

将来源于卵巢透明细胞腺癌的人肿瘤细胞系RMG-1细胞腹腔注射到裸鼠体内，发现从肠系膜肿瘤结节中获得的细胞形成了比原始RMG-1细胞更多、更大的肿瘤结节。RMG-1-h细胞在体内传代4次后从肿瘤结节中转移到培养物中，其播散潜力与直接从组织中播散的细胞一样高，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碳水化合物抗原的含量和表达。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，在RMG-1-h细胞的直方图中发现抗Le^x抗体弱阳性和中等阳性的细胞被消除，导致强烈表达Le^x的细胞富集，这可能是高传播潜力的原因。此外，经抗Le^x抗体预处理后，发现RMG-1细胞对间皮细胞的粘附明显受到抑制，表明Le^x介导卵巢癌细胞与间皮细胞之间的细胞间相互作用。通过tlc免疫染色，在RMG-1和RMG-1-h细胞中均检测到两种Le^x-糖脂，III^3Fuc α-nLc_4Cer和V^3Fuc α-nLc_6Cer，并且RMG-1-h细胞中Le^x-糖脂的疏水部分与RMG-1细胞不同。因此，卵巢癌细胞的高播散潜力被证明是由Le^x决定因子介导的，并且携带Le^x的细胞通过裸鼠体内反复传代而富集。

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.