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

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。

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.