Tanaka Kyoko, Mikami Mikio, Aoki Daisuke, Kiguchi Kazushige, Ishiwata Isamu, Iwamori Masao
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-8582.
Oncol Lett. 2010 Nov;1(6):1061-1066. doi: 10.3892/ol.2010.171. Epub 2010 Sep 9.
To identify glycolipid antigens associated with histologically defined types of ovarian carcinomas, we determined the amounts of α2,6-sialyl and Lewis-active glycolipids, the specific activities of the α2,3- and α2,6-sialyltransferases, and the gene expression of sugar transferases in mucinous and serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma tissues and cell lines derived from them. α2,6-sialyl glycolipid IV(6)NeuAcα-nLc(4)Cer detected with a newly developed monoclonal antibody, Y916, was present in 5/7 serous cystadenocarcinoma cases in relatively higher amounts than those in the other carcinoma tissues. On the other hand, the amounts of Lewis-active glycolipids in serous cystadenocarcinoma tissues were lower than those in the other carcinoma tissues. No correlation was observed between the structures of Lewis glycolipids and the histological classification. The gene expression of α2,3- and α2,6-sialyltransferases and α1,3/4-fucosyltransferase for the synthesis of Lewis-active glycolipids was not positively correlated with the amounts of the respective glycolipids, probably due to the epigenetic regulation of transferases in the overall metabolic pathways for lacto-series glycolipids. However, the amounts of GM3 and GD3 with short carbohydrate chains correlated with the relative intensities of GM3 and GD3 synthase gene expression, respectively. Among ovarian carcinoma-derived cell lines, the serous cystadenocarcinoma-derived ones exhibited a lower frequency of Lewis-active glycolipid expression than the other carcinoma-derived ones, which was similar to that in the respective tissues. Thus, malignancy-related Lewis-active glycolipids were shown to be regulated in different modes in ovarian serous cystadenocarcinomas and the other carcinomas.
为了鉴定与组织学定义的卵巢癌类型相关的糖脂抗原，我们测定了黏液性和浆液性囊腺癌、透明细胞腺癌和子宫内膜样癌组织及其衍生的细胞系中α2,6-唾液酸化和具有Lewis活性的糖脂的含量、α2,3-和α2,6-唾液酸转移酶的比活性以及糖转移酶的基因表达。用新开发的单克隆抗体Y916检测到的α2,6-唾液酸化糖脂IV(6)NeuAcα-nLc(4)Cer在7例浆液性囊腺癌病例中的5例中含量相对高于其他癌组织。另一方面，浆液性囊腺癌组织中具有Lewis活性的糖脂含量低于其他癌组织。未观察到Lewis糖脂结构与组织学分类之间的相关性。参与合成具有Lewis活性糖脂的α2,3-和α2,6-唾液酸转移酶以及α1,3/4-岩藻糖基转移酶的基因表达与相应糖脂的含量未呈正相关，这可能是由于乳系列糖脂整体代谢途径中转移酶的表观遗传调控所致。然而，具有短碳水化合物链的GM3和GD3的含量分别与GM3和GD3合酶基因表达的相对强度相关。在源自卵巢癌的细胞系中，源自浆液性囊腺癌的细胞系中具有Lewis活性的糖脂表达频率低于源自其他癌的细胞系，这与相应组织中的情况相似。因此，与恶性肿瘤相关的具有Lewis活性的糖脂在卵巢浆液性囊腺癌和其他癌中以不同模式受到调控。
