Elucidation for biological significance of cancer-associated carbohydrate antigens through genetic modification of carbohydrates

通过碳水化合物的基因修饰阐明癌症相关碳水化合物抗原的生物学意义

• 批准号: 10671215
• 负责人: WATANABE Masahiko
• 金额: $ 1.73万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671215/
• 关键词: STn antigen; CA19-9 antigen; Colon cancer; Liver metastasis; 糖鎖抗原; 糖転移酵素; 癌転移

Drastic alteration of carbohydrate antigens in carcinogenesis and metastasis were well-known phenomenon, and applied clinically as tumor markers. However, its molecular mechanism were hardly understood.In this project, we successfully cloned cDNAs for two novel glycosyltransferases, ST6GalNAc-I and β3Gal-T5, which were able to synthesize well-known cancer-associated antigens, sialyl Tn and CA19-9 respectively. The expression pattern of these enzymes were well correlated to that of respective antigens, strongly suggesting that these enzymes were physiological synthase of these cancer-associated antigens in the normal and cancer tissue.Thus, we transfected cDNAs of these enzymes into cells which did not express these antigens, and established several stable transformants, strongly expressing the antigens. Now we are investigating these cells for alteration of bilogical features both in vitro and in vivo models.

糖类抗原在肿瘤发生和转移过程中的急剧变化是众所周知的现象，并作为肿瘤标志物应用于临床。本课题成功克隆了两种新型糖基转移酶ST 6 GalNAc-I和β3Gal-T5的cDNA，这两种糖基转移酶分别能合成已知的肿瘤相关抗原sialyl Tn和CA 19 -9。这些酶的表达模式与各自抗原的表达模式有很好的相关性，强烈地表明这些酶是正常和癌组织中这些癌相关抗原的生理合成酶。因此，我们将这些酶的cDNA转染到不表达这些抗原的细胞中，并建立了几个稳定的转化子，强表达这些抗原。现在我们正在研究这些细胞在体外和体内模型中生物学特征的改变。

项目成果

S.ISSHIKI et.al.: "Cloning expression and characterization of a novel β3Gal T which is responsible for Lewis type 1 antiger incolor and pancreatic epithelin" J.Biol.Chem. (in press).

S.ISSHIKI 等人：“负责路易斯 1 型抗原颜色和胰腺上皮蛋白的新型 β3Gal T 的克隆表达和表征”J.Biol.Chem。

Ikehara Y et al.: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-alpha2,6-sialyltransferase(ST6GalNAc I):a candidate for synthesis of cancer-assoiated sialyl-Tn antigens"Glycobiology. 9(11). 1213-1224 (1999)

Ikehara Y 等人：“编码 N-乙酰半乳糖胺-α2,6-唾液酸转移酶 (ST6GalNAc I) 的人类基因的克隆和表达：用于合成癌症相关唾液酸-Tn 抗原的候选者”糖生物学。

Ikehara Y et al.: "Cloning and expression of a human gene encoding an ST6GalNAc: a candidate for synthesis of cancer-associated sialyl Tn antigens"Glycobiology. 9(11). 1213-1224 (1999)

Ikehara Y 等人：“编码 ST6GalNAc 的人类基因的克隆和表达：用于合成癌症相关唾液酸 Tn 抗原的候选者”糖生物学。

Ikehara Y et al: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-alpha2,6-sialytransferase (ST6GalNAc I): a candidate for synthesis of cancer-associated sialyl-Tn antigens"Glycobiology. 9(11). 1213-24 (1999)

Ikehara Y 等人：“编码 N-乙酰半乳糖胺-α2,6-唾液酸转移酶 (ST6GalNAc I) 的人类基因的克隆和表达：用于合成癌症相关唾液酸-Tn 抗原的候选者”糖生物学。

Isshiki S et al.: "Cloning, expression, and characterization of a novel β3Gal-T responsible for synthesis of type 1 chain in colorestal and pancreatic epithelia and tumor cells derived therefrom"J. Biol. Chem.. 274(18). 12499-12507 (1999)

Isshiki S 等人：“负责结直肠上皮细胞和胰腺上皮细胞以及源自其的肿瘤细胞中合成 1 型链的新型 β3Gal-T 的克隆、表达和表征”J. Biol. 12499。 -12507 (1999)