Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.99.6 (sialyltransferase)
1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell line MDA 886Ln was established from a laryngeal lymph node metastasis. When grown as a multicellular tumor spheroid (MTS), it exhibits squamous differentiation. We studied the effects of beta-all-trans retinoic acid (RA) on the growth, differentiation and glycoprotein content of this MTS model for squamous carcinomas of the head and neck. The growth of MTSs was inhibited in a dose-dependent manner by 10(-6) to 10(-10) M RA. Growth inhibition occurred between 3 and 5 days of RA treatment (10(-6)M). Immunohistochemical and electrophoretic analyses revealed that RA suppressed the morphological markers of squamous differentiation (squames), involucrin expression, and keratin expression. Gly-coprotein expression was examined by metabolic labelling using 3H-glucosamine, in situ labelling of polyacrylamide gels with 125I-labelled wheat-germ agglutinin (WGA), localization of fluorescein isothionate-WGA in frozen sections, and determination of sialyltransferase activity. Treatment using 10(-6) M RA altered glycoprotein expression both biochemically and morphologically, and WGA was shown to bind preferentially to sialic acid residues. The sensitivity of this MTS model to RA treatment and its ability to be analyzed through morphological, immunohistochemical and biochemical techniques suggest that it will prove useful in studying the relationships between growth, differentiation and RA-induced alterations in squamous carcinomas.
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PMID:Modulation of growth, differentiation and glycoprotein synthesis by beta-all-trans retinoic acid in a multicellular tumor spheroid model for squamous carcinoma of the head and neck. 247 9

In this study we report serum sialyltransferase and nucleoside diphosphatase activities of patients with malignant tumors of various primary sites and extent, prior to and during chemotherapy. Enzyme levels were compared to clinical and laboratory parameters. The sialyltransferase and uridine diphosphatase (UDPase) activities in samples of 43 patients with advanced ovarian cancer was four to ten fold above the normal mean value (sialyltransferase 85.1 +/- 58 pmol/hr/ml and UDPase 26.6 +/- 7.2 nmol/hr/ml). After effective chemotherapy with adriamycin and cisplatin, the enzyme activity decreased markedly. In cases of complete remission, enzyme activity decreased to the normal range. In three cases after initial response for several months a rise of both enzymes was observed before any other biochemical finding of the forthcoming relapse. Similar patterns were observed in testicular cancer (6 cases). Clinical correlation is also obvious in other tumors except malignant lymphomas. Our findings show that the activities of these enzymes correlated with the clinical course, and therefore they can be the basis for clinical application for tumor monitoring, especially during chemotherapy.
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PMID:Sialyltransferase and nucleoside diphosphatase as markers for tumor monitoring. 299 17

Galactosyltransferase (GalTF), sialyltransferase (SiaTF), fucosyltransferase (FucTF), 5'-nucleotidase (5'Nucl), and ADP-ribosyltransferase (RibTF) were determined in three subcellular fractions of tumor cells and adjacent control tissue from 20 patients with small primary infiltrating ductal adenocarcinomas of the breast. Viable, as pure tumor cell populations as possible were isolated, subfractionated, and their enzyme levels compared to those in the patients' sera. The activities in tumor cells of the three glycosyltransferases were two- to seven-fold higher, whereas 5'-Nucl and RibTF showed reduced activities when compared to adjacent noninvolved tissue. Serum GalTF and SiaTF were slightly elevated in early mammary carcinoma, whereas FucTF, 5'Nucl, and RibTF were decreased in comparison with a control group. The proposed tumor origin of circulating enzymes could not be confirmed. Surprisingly, only for RibTF could a correlation between tumor and serum activity be established; a weak correlation was found for SiaTF. However, no such relationship could be determined for GalTF, FucTF, or 5'Nucl. In conclusion, the enzyme profile of the tumor cell does not, except for RibTF, appear in the serum. Serum enzyme profiles, therefore, do not permit detection of the early stages of breast cancer. A high correlation between RibTF activity and cytosol estrogen and progesterone receptor levels has been determined in tumor cells, possibly indicating slower growing, more differentiated types of breast tumors.
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PMID:Enzyme activities in human breast tumor cells and sera. 299 19

Retinoic acid was found to increase the activity of cytidine monophosphosialic acid:lactosylceramide sialyltransferase activity in a nontransformed clonal hamster cell line, NIL 8, and a virally transformed clone, NIL 8-HSV. The potent tumor promoter phorbol-12-myristate-13-acetate (PMA) had no significant effect on sialyltransferase activity in NIL 8 cells but stimulated this activity almost 6-fold when added to NIL 8-HSV cells. There was a synergistically additive effect on sialyltransferase activity when PMA was added to NIL 8 cells in concert with retinoic acid. On the other hand neither PMA nor retinoic acid had an appreciable effect on two other glycosyltransferases measured, uridine diphospho-N-acetylgalactosamine:globotriaosylceramide N-acetylgalactosaminyl-transferase and uridine diphosphogalactose:asialoagalactofetuin galactosyltransferase. Examination of sialyltransferase activity in a human epidermoid carcinoma cell line showed a large increase in enzyme activity in response to retinoic acid administration. Two nontransformed hamster cell lines had less basal sialyltransferase activity but also showed marked elevations after retinoic acid treatment. It is proposed that one of the molecular mechanisms underlying the biological effects of retinoic acid and PMA may be an increase in sialyltransferase activity. Possible regulatory mechanisms are discussed.
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PMID:Effect of retinoic acid and phorbol-12-myristate-13-acetate on glycosyltransferase activities in normal and transformed cells. 310 23

As described previously (I. Kijima-Suda et al., Cancer Res., 46: 858-862, 1986), a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O- acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)ur idine (KI-8110), inhibits pulmonary metastasis of murine colon adenocarcinoma 26 sublines of high (NL-17) and low (NL-44) metastatic potential. To investigate the mechanism of this inhibition, the effect of KI-8110 on the metastatic cascade, especially on the interaction between tumor cells and platelets which may play a crucial role in tumor cell metastasis, was examined. NL-17 cells induced irreversible platelet aggregation in heparinized human platelet-rich plasma in vitro. This activity was reduced by pretreatment of the tumor cells with KI-8110. Inhibition of aggregation was also induced by the treatment of tumor cells with neuraminidase or Limax flavus agglutinin, a lectin specific for sialic acid. Sialic acid, fucose, sialyllactose, and bovine submaxillary mucin inhibited this tumor cell-induced platelet aggregation, while galactose, mannose, lactose, alpha 1-acid glycoprotein, fetuin, and asialo-bovine submaxillary mucin did not. KI-8110 also inhibited platelet-derived growth factor-dependent growth of NL-17 cells, but showed no effect on insulin or epidermal growth factor-dependent growth of the tumor cells. Platelet-derived growth factor-induced phosphorylation of membrane protein was reduced by treatment of NL-17 cells with KI-8110. The same result was obtained in the neuraminidase-treated membrane fraction of NL-17 cells. These results suggest that KI-8110 inhibits experimental tumor cell metastasis by inhibiting the interaction between tumor cells and host platelets in at least two pathways, and this may be due to a reduction of sialic acid contents of the membrane surface of tumor cells.
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PMID:Possible mechanism of inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid: nucleoside conjugate. 328 33

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

Numerous investigations suggest that cell surface glycoconjugates, and in particular sialic acids, are directly involved in determining the metastatic phenotype. To further evaluate this hypothesis, we have used a variety of techniques to probe the cell surfaces of several metastatic variants of the murine B16 melanoma that were selected for experimental lung-colonizing ability (Fidler, I. (1973) Nature 242, 148-149) or for their ability to spontaneously metastasize from the site of a subcutaneous injection (Stackpole, C. W., Alterman, A. L., and Fornabaio, D. M. (1985) Invasion & Metastasis 5, 125-142). Using a highly sensitive high performance liquid chromatography sialic acid assay in conjunction with Vibrio cholerae sialidase, we find that none of these metastatic variants differ significantly in their overall levels of cell surface sialic acid. Using highly purified, linkage-specific sialyltransferases, in conjunction with specific glycosidases, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we also find no significant differences between the efficient lung-colonizing variant, B16-F10 and the poorly-colonizing B16-F1 or B16-Flr variants. In contrast, the spontaneously metastatic variants examined contain substantially different levels of specific penultimate sialylation sites. The tumorigenic but nonmetastatic B16-LM3/G3.26 variant contains 4-fold more penultimate Gal beta 1-3GalNAc sialylation sites than the tumorigenic and highly metastatic B16-LM3/G3.12 variant when CMP[3H]NeuAc and the alpha 2-3Gal beta 1-3GalNAc sialyltransferase are used to probe the melanoma cell surfaces. Several prominent glycoconjugates of apparent Mr 43,000, 40,000, and 30,000 are especially evident upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the nonmetastatic cells. The nonmetastatic variant also contains 2-fold more Gal beta 1-4GlcNAc sialylation sites than the metastatic variant when the alpha 2-6Gal beta 1-4GlcNAc sialyltransferase is used as a cell surface probe. In this case, glycoconjugates of apparent Mr 74,000, 45,000, and 43,000 are more prominently observed on the cell surfaces of the nonmetastatic variant. These data indicate that the differences in lung-colonizing abilities of B16 melanoma metastatic variants do not correlate with the numbers or sialylation states of specific penultimate oligosaccharide structures on their surfaces. However, the relative levels of specific penultimate saccharide structures do correlate with the ability of the cells to undergo spontaneous metastasis from a subcutaneous tumor.
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PMID:Cell surface sialylation and tumor metastasis. Metastatic potential of B16 melanoma variants correlates with their relative numbers of specific penultimate oligosaccharide structures. 337 1

Neoplastic transformations are accompanied by an alteration in the composition of cell membrane glycoproteins, major structural components of the cell surface. Plasma sialyltransferase enzyme is involved in the transfer of sialic acid residues from cytosine monophosphate (CMP) sialic acid to a suitable acceptor. In the present study plasma sialyltransferase was assayed using a radiometric method, which measured the transfer of radioactivity from (14C) CMP sialic acid to desialated fetuin. Plasma sialyltransferase was measured in 127 normal and 91 cancer patients. The mean plasma sialyltransferase in the normal volunteers was 837 units (CPM/25 microliters plasma/hr). The mean plasma sialytransferase in 26 breast cancer patients, 22 lung cancer patients, 20 colon cancer patients, 5 ovarian cancer patients, 4 cervix cancer patients, 5 pancreas cancer patients, 6 prostate cancer patients, and 3 gastrointestinal tract cancer patients was 1710, 1406, 1344, 1227, 1233, 1406, 1250, and 1426 units, respectively. No significant difference was observed with respect to age. In 32 treated breast cancer patients the mean value was 757 units. Serial determinations in 17 patients correlated well with tumor burden. However, in 2 patients the plasma enzyme level did not correspond to tumor mass. These results indicate that plasma sialyltransferase is significantly elevated in patients with a variety of cancers. Plasma sialyltransferase determination may be useful in the followup of patients with a variety of cancers.
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PMID:Plasma sialyltransferase as a tumor marker. 339 Aug 43

The total and sialidase-releasable sialic acid contents of murine colon adenocarcinoma 26 sublines of high (NL-17) and low (NL-44) metastatic potential were found to be positively correlated with their ability to undergo metastasis. Furthermore, sialyltransferase activity of intact NL-17 cells was higher than that of NL-44 cells. These findings suggest that sialic acid on the cell surface may play a role in the metastasis of these cells. Therefore, the effect of a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O -acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)u ridine (Kl-8110), on the experimental lung metastasis of NL-17 or NL-44 cells was examined. Kl-8110 inhibited the transfer of sialic acid to its endogenous acceptor in NL-17 and NL-44 cells. NL-17 or NL-44 cells were injected into the tail veins of mice, and the metastasis-inhibiting activity of Kl-8110 was evaluated on the basis of both the lung weight and the number of pulmonary surface nodules about 3 wk after the tumor cell injection and of the survival ratio of mice inoculated with the tumor cells. Pretreatment of tumor cells with Kl-8110 together with i.v. injection of Kl-8110 caused significant inhibition of pulmonary metastasis of both NL-17 and NL-44 cells. Inhibition of metastasis and prolongation of survival were also observed on i.v. injection of Kl-8110 without pretreatment of the tumor cells with Kl-8110, but the degree of inhibition was lower than that in the case of the two treatments together. Kl-8110 itself had neither cytostatic nor cytotoxic effects on NL-17 and NL-44 but reduced the retention of tumor cells in the lungs. This antimetastatic effect of Kl-8110 may be due to modification of the tumor cell surface resulting from inhibition of sialyltransferase by Kl-8110. In addition, a beta-linked sialic acid:nucleoside conjugate (Kl-8111) and an equimolar mixture of Kl-8110 and Kl-8111 (Kl-414) also inhibited the metastatic ability of NL cells to the same extent as Kl-8110 did.
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PMID:Inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid:nucleoside conjugate having sialyltransferase inhibiting activity. 375 83

Sialyltransferase was measured in serum of normal and hepatoma Mc-29 bearing chickens. By preparative isoelectric focusing the multiple forms of sialyltransferase from both kind of serums was studied as well. By using influenza virus neuraminidase an attempt was made for partial structural characterization of the sialylation sites in asialofetuin applied as exogenous acceptor for sialyltransferase determination. It was established an elevated serum sialyltransferase activity in tumor bearing chickens with tumor an enzyme form was detected with pI-4.99 identical with an enzyme form described previously in solubilized plasma membrane preparations from hepatoma Mc-29. Monitoring of multiple forms of serum glycosyltransferases may be of value in answering the problem concerning the tissue origin of serum enzymes.
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PMID:Characterization of sialyltransferases from serum of normal and hepatoma Mc-29 bearing chickens. 395 42


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