Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas
Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas
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DOI：
10.1007/s10719-006-6979-6
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发表时间：
2006-07-01
影响因子：
3
通讯作者：
Yamashita, Katsuko
中科院分区：
文献类型：
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作者：
Kanoh, Akira;Seko, Akira;Yamashita, Katsuko
粘液性和透明细胞腺癌是卵巢上皮癌的主要组织学类型，由于对化疗的抵抗而导致预后不良。针对卵巢粘液性腺癌和透明细胞腺癌的新的肿瘤标志物将有助于克服这些严重的疾病。我们先前通过酶学鉴定和RT-PCR发现，结肠粘液腺癌组织异位表达6-O-磺基转移酶家族成员GlcNAc6ST-2(Seko，A.et al.(2002)糖生物学12,379-388)。在这里，我们制备了GlcNAc6ST-2特异性多克隆抗体用于免疫组织化学分析，发现GlcNAc6ST-2不仅在结肠粘液性腺癌中异位表达，而且在卵巢粘液性腺癌、透明细胞癌和乳头状浆液性腺癌中也有异位表达。相比之下，实性浆液性腺癌、子宫内膜样腺癌和粘液性腺瘤表达GlcNAc6ST-2的频率要低得多，甚至根本不表达。RT-PCR分析证实GlcNAc6ST-2转录本在卵巢粘液性腺癌中表达，而在粘液性腺瘤中不表达。免疫组织化学分析表明，卵巢腺癌细胞表达6-O-硫化葡聚糖，包括L-选择素配体及其相关的糖链。这些结果表明，GlcNAc6ST-2可能是一种新的肿瘤抗原，在卵巢粘液性、透明细胞和乳头状浆液性腺癌中特异表达。
Mucinous and clear cell adenocarcinomas are the major histological types of ovarian epithelial cancer and are associated with a poor prognosis due to their resistance to chemotherapy. A novel tumor marker specific for ovarian mucinous and clear cell adenocarcinomas would be helpful for overcoming these serious diseases. We showed previously by enzymological characterization and RT-PCR that colonic mucinous adenocarcinoma tissues ectopically express GlcNAc6ST-2, a member of the carbohydrate 6-O-sulfotransferase family (Seko, A. et al. (2002) Glycobiology 12, 379-388). Here, we prepared a GlcNAc6ST-2-specific polyclonal antibody for immunohistochemical analysis and found that GlcNAc6ST-2 is ectopically expressed by not only colonic mucinous adenocarcinomas but also ovarian mucinous, clear cell and papillary serous adenocarcinomas. In contrast, solid serous adenocarcinomas, endometrioid adenocarcinomas, and mucinous adenomas expressed GlcNAc6ST-2 much less frequently or not at all. RT-PCR analysis confirmed that GlcNAc6ST-2 transcripts are expressed in ovarian mucinous adenocarcinomas but not in mucinous adenomas. In addition, immunohistochemical analysis using sulfated glycan-specific monoclonal antibodies showed that ovarian adenocarcinoma cells express GlcNAc 6-O-sulfated glycans, including an L-selectin ligand and its related glycans. These results indicate that GlcNAc6ST-2 would be a novel tumor antigen that is specifically expressed in ovarian mucinous, clear cell and papillary serous adenocarcinomas.