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

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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.