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Specific Detection of Molecular Species of Glycosyltransferases Involved in Synthesis of Tumor Marker Carbohydrate Determinants.

特异性检测参与肿瘤标志物碳水化合物决定剂合成的糖基转移酶的分子种类。

基本信息

批准号：
09672371
负责人：
KANNAGI Reiji
金额：
$ 2.3万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Human cancers express cancer-associated carbohydrate determinants such as sialyl Lewis X or sialyl Lewis A, which serve as ligand for cell adhesion molecules of the selectin family, and thus involved in hematogenous metastasis of cancer. We investigated mRNA of fucosyltransferase (Fuc-T) and sialyltransferase (ST) isoenzymes, including Fuc-T III, IV, V.VI, VII, ST-3N, ST-30, ST3 Gal II and ST-4, in human colorectal cancer tissues by Northern blotting and RT-PCR.Regarding fucosyltransferases, mRNA of Fuc-T III and VI was not significantly altered, and only Fuc-T IV mRNA showed a significant increase in cancer tissues when compared with adjacent non-malignant colonic epithelia. Concerning sialyltransferase isoenzyme, mRNA for ST-3N remained unchanged, whereas that for ST-4 decreased significantly in cancer tissues (P<O.005). The most remarkable finding was that the messages of ST-30 and ST3 Gal II were prominently increased in cancer tissues as compared with non-malignant colorectal mucosa (P<O.OOO1 and P<O.OO1, respectively). We have also shown that the NCC-ST-439 antibody, which detects a tumor-associated carbohydrate antigen in breast, gastric and colon cancers and is widely used for serum diagnosis of these cancers, recognizes NeuAcalpha2*3Galbeta1*4(Fucalpha1*3)GlcNAcbeta1 *6Ga1Nacalpha1*R, the sialyl Lewis X on the mucin GlcNAcbeta1*6GalNAcalpha structure. We detected sialyl 6-sulfo Lewis X is also expressed in colonic tissues. Its expression was significantly stronger in non-malignant mucous membranes than in cancer tissues, suggesting that the responsible 6-sulfotransferase is down-regulated upon malignant transformation.

人类癌症表达癌症相关的碳水化合物决定簇，例如唾液酸刘易斯X或唾液酸刘易斯A，其充当选择素家族的细胞粘附分子的配体，并因此参与癌症的血行转移。本研究采用北方印迹和RT-PCR方法检测了人大肠癌组织中岩藻糖基转移酶（Fuc-T）和唾液酸转移酶（ST）同工酶（Fuc-T III、IV、V、VI、VII、ST-3 N、ST-30、ST-3 Gal II和ST-4）的mRNA。与癌旁正常结肠上皮相比，只有Fuc-T IV mRNA在癌组织中表达显著增加。唾液酸转移酶同工酶中，ST-3 N的mRNA在癌组织中无变化，而ST-4的mRNA在癌组织中显著降低（P<0.005）。最显著的发现是ST-30和ST 3 Gal II在癌组织中的表达显著高于非癌组织（P<0.0001和P<0.001）。我们还发现，NCC-ST-439抗体可检测乳腺癌、胃癌和结肠癌中的肿瘤相关碳水化合物抗原，并广泛用于这些癌症的血清诊断，该抗体可识别NeuAcalpha 2 * 3Galbeta 1 *4（Fucalpha 1 *3）GlcNAcbeta 1 * 6 Ga 1 Nacalpha 1 *R，即粘蛋白GlcNAcbeta 1 * 6 GalNAcalpha结构上的唾液酸刘易斯X。我们检测到唾液酸6-磺基刘易斯X也在结肠组织中表达。它的表达在非恶性粘膜中比在癌组织中显著更强，表明负责的6-磺基转移酶在恶性转化后下调。