Detection of glycoproteins as tumor-associated Hanganutziu-Deicher antigen in human gastric cancer cell line, NUGC4

Fukui, Yuichi; Maru, Morimasa; Ohkawara, Ken-ichi; Miyake, Tamotsu; Osada, Yoshio; Wang, Daqing; Ito, Tetsuya; Higashi, Hideyoshi; Naiki, Masaharu; Wakamiya, Nobutaka; Kato, Shiro

doi:10.1016/s0006-291x(89)80123-8

Cited by 25 publications

(7 citation statements)

References 11 publications

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“…It is generally stated that sialic acid is not found in insects; conclusive evidence has now been presented for its presence in Drosophila melanogaster through all stages of development [ 1401. N-Glycoloylneuraminic acid (NeuGc), once believed to be confined to pigs and horses, has now been found in most animals, except [141,1421. The existence of these antigens has raised the possibility that the gene responsible for the synthesis of N-glycoloylneuraminic acid (by hydroxylation of CMP-NeuAc to CMP-NeuGc) is suppressed under normal conditions in humans, but may be induced in the course of oncogenesis.…”

Section: Monosaccharide Constituentsmentioning

confidence: 99%

Protein glycosylation

Lis

Sharon

1993

European Journal of Biochemistry

813

479

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During the last decade, there have been enormous advances in our knowledge of glycoproteins and the stage has Keen set for the biotechnological production of many of them for therapeutic use. These advances are reviewed, with special emphasis on the structure and function of the glycoproteins (excluding the proteoglycans). Current methods for structural analysis of glycoproteins are surveyed, as are novel carbohydrate-peptide linking groups, and mono-and oligo-saccharide constituents found in these macromolecules. The possible roles of the carbohydrate units in modulating the physicochemical and biological properties of the parent proteins are discussed, and evidence is presented on their roles as recognition determinants between molecules and cells, or cell and cells. Finally, examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.Among the different types of covalent modifications that newly synthesized proteins undergo in living organisms, none is as common as glycosylation [l-61. It is also the most diverse, both with respect to the kinds of amino acid that are modified and the structures attached. The origins for this diversity are chemical as well as biological. The former results from the ability of monosaccharides to combine with each other in a variety of ways that differ not only in sequence and chain length, but also in anomery (a or p), position of linkages and branching points. Further structural diversification may occur by covalent attachment of sulfate, phosphate, acetyl or methyl groups to the sugars. Therefore, in theory, an enormous variety of glycans, both oligosaccharides and polysaccharides, can be generated from a relatively limited number of monosaccharides. Biological diversity derives from the fact that, whereas proteins are primary gene products, glycans are secondary gene products. As a result, glycosylation is species-and cell-specific, and is determined as well by the structure of the protein backbone and the carbohydrate attachment site. This means that glycosylation of any protein is dependent on the cell or tissue in which it is produced and that the polypeptide encodes information that directs its own pattern of glycosylation.In an individual glycoprotein more than one carbohydrate unit is often present, attached at different positions by either an N-linkage, an 0-linkage or both. Moreover, each attachCorrespondence to N. Sharon,

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Section: Monosaccharide Constituentsmentioning

confidence: 99%

Protein glycosylation

Lis

Sharon

1993

European Journal of Biochemistry

813

479

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“…In general, the NeuGc residue is not expressed in human and chicken normal tissues, but it is widely present in other vertebrates [6,7]. In contrast, it has been reported that anti-NeuGc-containing ganglioside antibodies recognize some human tumours and cancerous cell lines [8,9]. These studies have been carried out using polyclonal or monoclonal antibodies from chicken [10], human [11], or murine origin [12], but in all these tumours minimal levels of NeuGc were reported.…”

Section: Introductionmentioning

confidence: 99%

Clinical evidences of GM3 (NeuGc) ganglioside expression in human breast cancer using the 14F7 monoclonal antibody labelled with 99mTc

Oliva

Valdés

Casacó

et al. 2005

Breast Cancer Res Treat

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The relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, reasons for considering these molecules as potential targets for cancer immunotherapy and diagnosis. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast tumours. Nevertheless, the lack of a direct evidence of this antigenic display in human breast cancer has kept the subject controversial. For the first time, we described herein the "in vivo" detection of GM3(NeuGc) ganglioside in human breast primary tumours using a radioimmunoscintigraphic technique with 14F7, a highly specific anti-GM3(NeuGc) ganglioside monoclonal antibody, labelled with (99m)Tc. In an open, prospective Phase I/II clinical trial, including women diagnosed in stage II breast cancer, the 14F7 monoclonal antibody accumulation in tumours at doses of 0.3 (n=5), 1 (n=5) and 3 mg (n=4) was evaluated. Noteworthy, the immunoscintigraphic study showed antibody accumulation in 100% of patients' tumours for the 1 mg dose group. In turn, the radioimmunoconjugate injected at doses of 0.3 mg or 3 mg of the antibody, was uptaken by 60 and 33.3% of breast tumours, respectively. "In vivo" immune recognition of GM3(NeuGc) in breast tumours reinforces the value of this peculiar target for cancer immunotherapy.

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“…Evidence is also available to suggest that certain cancerous states may induce NeuSGc incorporation, as observed in rat mammary adenocarcinoma cell lines [lo] and in rat colon tumours [ll]. Furthermore, there are a large number of reports which indicate that small amounts of NeuSGc are present in antigenic gangliosides [12, 131 or glycoproteins [14] of certain human tumour cells. This raises the possibility that cell transformation causes the induction of an otherwise quiescent NeuSAc hydroxylase gene.…”

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confidence: 99%

A study on the regulation of N‐glycoloylneuraminic acid biosynthesis and utilization in rat and mouse liver

Lepers

Shaw

Schneckenburger

et al. 1990

European Journal of Biochemistry

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The relative contribution of N-glycoloyl-P-D-neuraminic acid (NeuSGc) to total sialic acids expressed in mouse and rat liver glycoconjugates was found to be 95% and 11%, respectively. This considerable difference in sialic acid composition made these two tissues suitable models for a comparative investigation into the regulation of NeuSGc biosynthesis and utilization.An examination of the CMP-glycoside specificity of Golgi-associated sialyltransferases using CMP-N-acetylp-D-neuraminic acid (CMP-NeuSAc) and CMP-NeuSGc revealed no significant tissue-dependent differences. The Golgi membrane CMP -sialic acid transport system from rat liver did, however, exhibit a slightly higher internalisation rate for CMP-NeuSAc, though no preferential affinity for this sugar nucleotide over CMP-NeuSGc was observed.In experiments, where Golgi membrane preparations were incubated with an equimolar mixture of labelled CMP-NeuSAc and CMP-NeuSGc, no significant tissue-dependent differences in [14C]sialic acid composition were observed, either in the luminal soluble sialic acid fraction or in the precipitable sialic acid fraction, results which are consistent with the above observations. From this experiment, evidence was also obtained for the presence of a Golgi-lumen-associated CMP -sialic acid hydrolase which exhibited no apparent specificity for either CMPNeuSAc or CMP-NeuSGc.The specific activity of the CMP-NeuSAc hydroxylase, the enzyme responsible for the biosynthesis of NeuSGc, was found to be 28-fold greater in high-speed supernatants of mouse liver than of rat liver. No hydroxylase activity was detected in the Golgi membrane preparations. It is therefore proposed that the cytoplasmic ratio of CMPNeuSAc and CMP-NeuSGc produced by the hydroxylase, remains largely unmodified after CMP-glycoside uptake into the Golgi apparatus and transfer on to growing glycoconjugate glycan chains. The close relationship between the total sialic acid composition and the sialic acid pattern in the CMP-glycoside pools of the tissues lends considerable weight to this hypothesis.

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Detection of glycoproteins as tumor-associated Hanganutziu-Deicher antigen in human gastric cancer cell line, NUGC4

Cited by 25 publications

References 11 publications

Protein glycosylation

Protein glycosylation

Clinical evidences of GM3 (NeuGc) ganglioside expression in human breast cancer using the 14F7 monoclonal antibody labelled with 99mTc

A study on the regulation of N‐glycoloylneuraminic acid biosynthesis and utilization in rat and mouse liver

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