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

人类癌症表达肿瘤相关碳水化合物决定因子，如唾液酸化Lewis X或唾液酸化Lewis A，它们作为选择素家族细胞黏附分子的配基，从而参与癌症的血道转移。我们用Northern印迹和RT-PCR方法研究了人结直肠癌组织中岩藻糖基转移酶(Fuc-T)和唾液酸基转移酶(ST)同工酶(Fuc-T III、IV、V.VI、VII、ST-3N、ST-30、ST3 Gal II和ST-4)的mRNA表达。对于岩藻糖基转移酶，癌组织中Fuc-T III和VI的mRNA没有明显变化，只有Fuc-T IV的mRNA与癌旁非恶性结肠上皮组织相比显著增加。在唾液酸转移酶同工酶方面，癌组织中ST-3N的mRNA无明显变化，而ST-4的mRNA显著降低(P<0.005)。最显著的发现是癌组织中ST-30和ST3 Gal II的表达显著高于非恶性结直肠黏膜(P&lt；0.0001和P&lt；0.OOO1)。我们还发现，在乳腺癌、胃癌和结肠癌中检测肿瘤相关碳水化合物抗原的NCC-ST-439抗体，广泛用于这些癌症的血清诊断，识别NeuAcalpha2*3Galbeta1*4(Fucalpha1*3)GlcNAcbeta1*6Ga1Nacalpha1*R，粘蛋白GlcNAcbeta1*6GalNAcalpha结构上的唾液酸路易斯X。我们检测到唾液酸基6-磺基Lewis X也在结肠组织中表达。它在非恶性粘膜中的表达明显强于在癌组织中的表达，这表明负责的6-磺基转移酶在恶性转化过程中下调。

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.