Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In forty-one carcinomas and sixteen benign lesions (fibroadenoma and mastopathy) of the human breast, immunohistochemical expression of sialylated and non-sialylated forms of both Lea and Lex, and the A, B, and H type 2 blood group substances were studied by using an indirect immunoperoxidase staining. In normal ductal epithelium and benign lesion of breast, Lewis-related antigens were mostly expressed. Breast carcinomas showed these antigens with the following frequencies: Lea, 31.7% (13/41); sialyl Lea, 56.1% (23/41); Lex, 46.3% (19/41); sialyl Lex, 68.3% (28/41); A/B/H type 2, 38.1% (16/41). Sialylated forms of Lea and Lex were observed more frequently than their respective non-sialylated forms in breast carcinomas. In both one normal epithelium and four carcinomas of breast with Le(a-b-) phenotype, the expressions of type 2 antigens were observed, while type 1 antigens were not consistently expressed. Although compatible expression was observed in all specimens of both normal epithelium and benign lesion of breast, twenty-four cases with the deletion of A and/or B antigens, six cases with H type 2 accumulation and one case with incompatible expression were demonstrated in breast carcinoma. Thirty-one breast carcinomas which showed the deletion of A/B/H type 2 expressed the Lewis-related antigens more frequently than nine cases which showed compatible expression. These results suggested that the activation of terminal fucosyltransferase and sialyltransferase as well as inactivation of some glycosyltransferases had occurred in cancer cell membrane, and sialyl Lex, defined by a new monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen independent of Lewis blood group type in breast cancer.
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PMID:Immunohistochemical expression of blood group substances and related carbohydrate antigens in breast carcinoma. 190 2

The expression of antigens of the blood group Lewis a/b family were studied in a series of 42 prostatectomy specimens from patients with adenocarcinoma clinically confined to the prostate; 19 of these were later reclassified as pathologic Stage C. Staining of normal or hyperplastic versus neoplastic epithelium was assessed in routinely processed, paraffin-embedded tissue using murine monoclonal antibodies and an avidin-biotin immunoperoxidase technique. Antigens screened and the antibodies used to recognize them were Lewis a (CF4C4), Lewis b and Type 1 H (NS10), monosialosyl Lewis a I (19.9), and disialosyl Lewis a and monosialosyl Lewis a II (FH7). FH7 strongly stained the benign epithelium of all 39 Lewis positive cases, suggesting that the sialyltransferase responsible for synthesis of FH7-reactive determinants is highly active in benign prostatic tissue. When compared to the reactivity of benign epithelium in Lewis positive cases, the staining of the carcinomas was markedly reduced in 18 cases (46%) and absent in 16 cases (41%). This reduction or loss of staining of the malignant epithelium was observed for all antibodies that stained the corresponding benign epithelium of each case. In only five of the cases (13%) was the intensity of staining in the carcinoma equal to that of the surrounding benign epithelium. No cases in this latter group had recurrence of disease, whereas in the other staining groups 25-33% of the cases had recurrences; median follow-up for the entire group was 78 months. No correlation was apparent between Gleason score and the staining pattern with these antigens. In summary, antigens of the Lewis a/b family are deleted in a high percentage of cases of prostatic adenocarcinoma.
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PMID:Deletion of antigens of the Lewis a/b blood group family in human prostatic carcinoma. 245 82

The isomeric sialyl-Lea-terminating pentasaccharide derivatives, alpha-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-[alpha-L-Fucp-(1 ----4)]-beta- D-GlcpNAc-(1----3)-beta-D-Galp-O(CH2)8COOMe and alpha-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-[alpha-L-Fucp-(1 ----4)]- beta-D-GlcpNAc-(1----6)-beta-D-Galp-O(CH2)8COOMe, have been prepared by the action in sequence of a porcine submaxillary (2----3)-alpha-sialyltransferase and a human-milk (1----3/4)-alpha-fucosyltransferase on the chemically synthesized trisaccharides beta-D-Galp-(1----3)-beta-D-GlcpNAc-(1----3)- and -(1----6)-beta-D-Galp- O(CH2)8COOMe, respectively.
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PMID:Enzymic synthesis of oligosaccharides terminating in the tumor-associated sialyl-Lewis-a determinant. 279 Aug 38

The CA 19-9 antigen is a monosialosyl Lea blood group antigen which has been shown to be a useful tumor-associated antigen for the diagnosis of gastrointestinal cancers. Recently, a sialylated derivative of this antigen, disialosyl Lea, was isolated from a colon cancer liver metastasis and a monoclonal antibody (FH7) recognizing this novel determinant was developed. The present study simultaneously compared the expression of Lea, monosialosyl Lea, and disialosyl Lea antigens in a variety of nonmalignant, premalignant, and malignant tissues of the colorectum and pancreas with an aim toward elucidating whether disialosyl Lea is expressed as a tumor-associated antigen. In normal colonic mucosa, disialosyl Lea expression closely resembled Lea expression in overall frequency, segmental distribution, and cellular localization whereas monosialosyl Lea (CA 19-9) was essentially absent. Along the crypt axis, Lea was more often expressed in goblet cells of the upper crypt whereas disialosyl Lea was found in goblet cells along the entire crypt. Fetal colonic mucosa expressed all three antigens, as did most colorectal cancers regardless of location within the colon or degree of differentiation. The majority of hyperplastic polyps and practically all adenomatous polyps also expressed these three antigens, and in adenomas, antigen expression was independent of polyp size, villous morphology, or degree of dysplasia. In the normal pancreas, the three antigens were expressed on ductal, ductular and centroacinar cells of all specimens. The majority of pancreatic cancers expressed all three antigens. Thus, in the normal colon, the absence of monosialosyl Lea (CA 19-9) in the presence of disialosyl Lea suggests that an alpha 2,6 sialyltransferase is active, which results in the masking of CA 19-9 antigen expression. These results further support the concept that specific sialyltransferases play a role in regulating the expression of tumor-associated antigens.
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PMID:Immunohistochemical comparison of Lea, monosialosyl Lea (CA 19-9), and disialosyl Lea antigens in human colorectal and pancreatic tissues. 328 36

A cancer-associated glycolipid antigen defined by monoclonal antibody 19-9 has the structure NeuAc alpha 2-3Gal Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-Cer. We have (formula; see text) studied its biosynthesis by testing the capacity of a crude microsomal fraction of SW 1116 cells to catalyze the addition of fucosyl or sialyl residues from GDP-fucose or CMP-sialic acid to glycolipid or oligosaccharide precursors. When the tetrasaccharide NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (LSTa) is incubated with GDP-[14C]fucose and SW 1116 microsomes, a 14C-labeled oligosaccharide is formed that can be separated from the incubation mixture on an affinity column containing antibody 19-9 bound to protein A-Sepharose. The product migrates slower than LSTa when analyzed by paper or thin-layer chromatography. After treatment with neuraminidase, it co-migrates with the pentasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (formula; see text) (LNF II) in both chromatographic systems. Similar experiments demonstrate that SW 1116 microsomes catalyze the addition of a sialyl residue to the tetrasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc to form LSTa. However, when LNF II is incubated with CMP-[14C]sialic acid and SW 1116 microsomes, no 19-9-active product is detected by affinity chromatography or by paper or thin-layer chromatography. Results using glycolipid precursors are consistent with these findings and also demonstrate the presence of the Lewis fucosyltransferase in SW 1116 cells. Thus, the biosynthesis of the sialyl-Lea antigen proceeds by addition of sialic acid to a type 1 precursor chain by a sialyltransferase, followed by addition of fucose by the Lewis fucosyltransferase.
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PMID:Biosynthesis of the cancer-associated sialyl-Lea antigen. 401 78

Monoclonal antibodies produced after immunization of mice with human melanomas define protein antigens expressed not only by melanomas by also by other tumours of neural crest origin such as astrocytomas and neuroblastomas. Other monoclonal antibodies react with antigens expressed by melanomas and fetal but not adult human melanocytes. Cells of common naevi and of precancerous lesions such as dysplastic naevi share many antigens with melanomas but not with normal melanocytes. Unlike melanomas, naevi in tissue culture are characterized by a finite lifetime. Factors that are instrumental in malignant transformation of dysplastic naevi in vivo and are apparently lacking in the tissue culture system are currently under study. Monoclonal antibodies produced after immunizing mice with cells of human gastrointestinal carcinomas define glycolipid antigens. The carbohydrate structure of one of these antigens is lacto-N-fucopentaose III. This antigen is very strongly expressed by a variety of human tumours and in the immunoperoxidase assay the respective monoclonal antibody also binds to normal human epithelium. Another monosialoganglioside is an antigen expressed by cells of gastrointestinal tract tumours such as of the pancreas, stomach and large bowel and by cells of villous adenomas of the colon, but not by cells of normal colonic mucosa. Its carbohydrate is a sialylated Lea-active pentasaccharide (sialylated lacto-N-fucopentaose II). A hitherto undiscovered sialyltransferase, which may be involved in synthesis of this antigen from Lewis A glycolipid, is probably active in tumour tissue and at early stages of embryogenesis but not in normal adult tissue. Human tumours implanted in mice are destroyed by monoclonal antibodies showing binding specificities for the implanted tumour. Only monoclonal antibodies of IgG2a isotype show tumoricidal activity. Destruction of the tumour is mediated by macrophages which adsorb the IgG2a monoclonal antibody to an Fe receptor. The tumours can also be destroyed, in the presence of monoclonal antibodies, by human monocytes, which after maintenance in culture fore two weeks develop Fc receptors for mouse IgG2a antibody.
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PMID:Embryonic precancerous and cancerous human antigens recognized by monoclonal antibodies. 634 4

Sialyl Lewis a/sialyl Lewis x antigens, which panels of monoclonal antibodies can recognize, are synthesized by a series of glycosyltransferases. Especially, alpha (1,3)/(1,4) fucosyltransferases and/or alpha(2,3)sialyltransferases regulate expression patterns temporally and spatially, such as in epithelium of digestive systems or in leukocytes. The carbohydrate ligands of P-selectin and E-selectin have been identified as sialyl Lewis x expressed on granulocytes, monocytes, and natural killer cells. Expression of sialyl Lewis x on these cells is mainly determined by Fuc-TVII, but as for the counterparts of sialyl-transferases, there remains much uncertainty. P-selectin-dependent adhesion of tumor cells and E-selectin-dependent adhesion of tumor cells to endothelial cells play some role for tumor cell aggregation leading to microembolism and hematogenous metastasis of cancers. We have found expression of some fucosyltransferases (Fuc-TIII, VI, VII) and a sialyltransferase (ST3O) are increased in colon cancer tissues coincidentally with sialyl Lewis a antigens, with which E-selectin can interact. As already started in many laboratories, genetic manipulation of glycosylation pathways in gene-targeted animals has an outstanding potential to yield clues to oligosaccharide function.
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PMID:[Structures, synthesis and functions of sialyl Le(a)/sialyl Le(x) antigens]. 763 14

A human colonic adenoma cell line PC/AA derived from a familial polyposis coli patient was passaged in culture to form an intermediate premalignant clonogenic variant AA/C1 and, upon treatment with differentiating and carcinogenic agents, a cell line AA/C1/SB10 which is tumourigenic in nude mice. These three mucin-secreting cell lines have been used as a model to study the changes in O-glycan biosynthesis during the progression to cancer. Several glycosyltransferases involved in the synthesis, elongation and termination of the common O-glycan core structures were found to decrease in the progression sequence towards adenocarcinoma. Higher activity of a number of enzymes was seen in the intermediate cell line. O-glycan biosynthesis in the original PC/AA cell line was closest to the normal human colonic phenotype, since all four common mucin O-glycan cores and their extended structures could be synthesized; core 3 beta 3-GlcNAc-transferase and alpha 6-sialytransferase acting on GalNAc-mucin were still detectable and core 2 beta 6-GlcNAc-transferase activity was accompanied by core 4 and I beta 6-GlcNAc-transferase activities. During progression towards adenocarcinoma, the expression of alpha 6-sialyltransferase, core 3 beta 3-GlcNAc-transferase, core 4 and I beta 6-GlcNAc-transferases were turned off. Using monoclonal antibodies, Tn antigen, sialyl-Tn antigen, O-acetyl-sialomucin and sialyl-Lea determinants were not detected in secreted or cellular mucin isolated from any of the cell lines. The exposure of MUC1 epitopes was seen in the malignant line, whereas sialyl-Lex determinants were found only in the premalignant PC/AA line. Sulfotransferase activities using core 1 substrate, Gal beta 1-3GalNAc alpha-benzyl, were high in PC/AA cells and progressively decreased upon development to adenocarcinoma, and this decrease correlated with mucin sulfation. In summary, the synthesis of less abundant, sialylated, fucosylated and extended, unbranched core 1 structures should be facilitated in the malignant cells. This is the first report of glycosyltransferase changes in human premalignant cells developing to tumourigenic cells. The data demonstrate that these cell lines are an excellent model to study the changes and regulation of mucin oligosaccharide biosynthesis during progression to cancer.
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PMID:O-glycan biosynthesis in human colorectal adenoma cells during progression to cancer. 802 Apr 79

The adhesion of circulating cancer cells to vascular endothelium is an important step in the hematogenous metastasis of cancer. Until recently, it has been believed that carbohydrate antigens are expressed on cancer cells, and E-selectin is expressed on endothelial cells to effect this adhesion. We investigated the gene expression of fucosyl-transferase (Fuc-T) and sialyltransferase (ST), which are involved in the synthesis of sialyl Lewisx (s-Lex) in breast cancer by using Northern blot analysis. The concentration of s-Lex in the cancerous portion was increased, compared to that in the adjacent non-cancerous portion. A correlation was found between the concentration of s-Lex and the amount of Fuc-T VI message in 9 cases of breast cancer tissue. Expression of the Fuc-T III message was found in only one case who expressed s-Lea. No expression of the Fuc-T V or VII message was observed. There was no relationship between the concentration of s-Lex and the amount of ST3N and ST4 transcripts. Similar findings were obtained from an analysis using cell lines derived from human breast cancer. When Fuc-T VI gene was transfected to MCF-7 cells, the expression of s-Lex was markedly induced on MCF-7 cells, and the attachment of cancer cells to endothelial cells was enhanced. These findings suggest that Fuc-T VI is chiefly involved in the synthesis of s-Lex on breast cancer cells.
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PMID:Gene expression of fucosyl- and sialyl-transferases which synthesize sialyl Lewisx, the carbohydrate ligands for E-selectin, in human breast cancer. 953 43

Lewis b (Leb) antigens are gradiently expressed from the proximal to the distal colon, i.e., they are abundantly expressed in the proximal colon, but only faintly in the distal colon. In the distal colon, they begin to increase at the adenoma stage of cancer development and then increase with cancer progression. We aimed to clarify the molecular basis of Leb antigen expression in correlation with the expression of other type I Lewis antigens, such as Lewis a (Lea) and sialylated Lewis a (sLea), in colon cancer cells. Considering the Se genotype and the relative activities of the H and Se enzymes, the amounts of Leb antigens were proved to be determined by both the H and Se enzymes in noncancerous and cancerous colon tissues. But the Se enzyme made a much greater contribution to determining the Lebamounts than the H enzyme. In noncancerous colons, the Se enzyme were gradiently expressed in good correlation with the Leb expression, while the H enzyme was constantly expressed throughout the whole colon. In distal colon cancers, the H and Se enzymes were both significantly upregulated in comparison with in adjacent noncancerous tissues. In proximal colon cancers, expression of the H enzyme alone was highly augmented. The augmented expression of Leb antigens in distal colon cancers is caused mainly by upregulation of the Se enzyme and partly by the H enzymes, while it is caused by upregulation of the H enzyme alone in proximal colon cancers. The Se gene dosage profoundly influences the amounts of the Leb, Lea, and sLea antigens in whole colon tissues, regardless of whether they are noncancerous or cancerous tissues. It suggests that the Se enzyme competes with alpha2,3 sialyltransferase(s) and the Le enzyme for the type I acceptor substrates.
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PMID:Molecular mechanisms of expression of Lewis b antigen and other type I Lewis antigens in human colorectal cancer. 1033 94


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