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

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。

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.