Detection of Gangliosides as <i>N</i>‐Glycolylneuraminic Acid‐specific Tumor‐associated Hanganutziu‐Deicher Antigen in Human Retinoblastoma Cells

Higashi, Hideyoshi; Sasabe, T; Fukui, Yuichi; Maru, Morimasa; Kato, Shiro

doi:10.1111/j.1349-7006.1988.tb00060.x

Cited by 57 publications

(41 citation statements)

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“…Because human cells are known to lack the enzyme CMP-NeuAc hydroxylase required for the synthesis of NeuGc, the NeuGc present on cancer cells has been regarded to be acquired from the external milieu, because human cancer cells cultured in vitro with FCS or transplants in nude/SCID mice more frequently contain NeuGc (40)(41)(42). The expression of NeuGc-G M2 in LS174T cells was thought to be due to the incorporation of NeuGc from the DMEM culture medium supplemented with 10% FCS, which is known to contain free NeuGc (38).…”

Section: Resultsmentioning

confidence: 99%

“…Later, it was found to be widely associated with common tumors including colon, stomach, liver, breast, ovary, and germ cell cancers (25,36,(46)(47)(48)(49). Among the cancer-associated gangliosides, G M2 is known to have a particularly high ability to elicit humoral immune response in humans, when conjugated with KLH and introduced with appropriate adjuvants (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…G M2 ganglioside, as well as other monosialogangliosides in humans, contains one N-acetyl sialic acid (NeuAc) residue. On the other hand, non-human sialic acid, N-glycolyl sialic acid (NeuGc), is also known to preferentially appear on cancer cells (23)(24)(25)(26). Carbohydrate determinants containing N-glycolyl sialic acid are synthesized by CMP-NeuAc hydroxylase (27,28), which is active in cells and tissues of various animals except humans.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxic Culture Induces Expression of Sialin, a Sialic Acid Transporter, and Cancer-Associated Gangliosides Containing Non–Human Sialic Acid on Human Cancer Cells

et al. 2006

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Tumor hypoxia figures heavily in malignant progression by altering the intracellular glucose metabolism and inducing angiogenic factor production, thus, selecting and expanding more aggressive cancer cell clones. Little is known, however, regarding hypoxia-induced antigenic changes in cancers. We investigated the expression of N-glycolyl sialic acid (NeuGc)-G M2 , a cancer-associated ganglioside containing non-human sialic acid, NeuGc, in human cancers. Cancer tissues prepared from patients with colon cancers frequently expressed NeuGc-G M2 , whereas it was virtually absent in nonmalignant colonic epithelia. Studies on cultured cancer cells indicated that the non-human sialic acid was incorporated from culture medium. Hypoxic culture markedly induced mRNA for a sialic acid transporter, sialin, and this accompanied enhanced incorporation of NeuGc as well as N-acetyl sialic acid. Transfection of cells with sialin gene conferred accelerated sialic acid transport and induced cell surface expression of NeuGc-G M2 . We propose that the preferential expression of NeuGc-G M2 in cancers is closely associated with tumor hypoxia. Hypoxic culture of tumor cells induces expression of the sialic acid transporter, and enhances the incorporation of non-human sialic acid from the external milieu. A consequence of this is the acquisition of cancer-associated cell surface gangliosides, typically G M2 , containing nonhuman sialic acid (NeuGc), which is not endogenously synthesized through CMP-N-acetyl sialic acid hydroxylase because humans lack the gene for the synthetic enzyme. As hypoxia is associated with diminished response to radiotherapy and chemotherapy, NeuGc-G M2 is a potential therapeutic target for hypoxic cancer cells. (Cancer Res 2006; 66(6): 2937-45)

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypoxic Culture Induces Expression of Sialin, a Sialic Acid Transporter, and Cancer-Associated Gangliosides Containing Non–Human Sialic Acid on Human Cancer Cells

et al. 2006

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“…For instance, Nakarai et al (35) found increased levels of both IgM and IgG antibodies against N-glycolylneuraminic acid-containing structures in sera from melanoma patients, but the presence of corresponding structures in glycolipid extracts from melanoma tumors seems to be controversial. The occurrence of tumor-associated ganglioside antigens with Hanganutziu-Deicher antigenic activity on human melanomas has been reported (36,37), but recent studies of the ganglioside composition of tumors from melanoma patients showing serological responses against N-glycolylneuraminic acid containing gangliosides have demonstrated that this structure is not found in melanomas (Portoukalian J, Tai T, pers. comm.).…”

Section: Gangliosides As Immunotherapeutic Targetsmentioning

confidence: 99%

Generation of Human Monoclonal Antibodies Against Ganglioside Antigens and Their Applications in the Diagnosis and Therapy of Cancer

Alfonso

Zeuthen

1996

Acta Oncologica

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“…NeuGc has been reported in human cancer [17,181 but not in normal tissues. However, there is a single report on the occurrence of trace levels of NeuGc in normal human tissues [28].…”

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confidence: 99%

Purification and characterization of N‐glycolylneuraminic‐acid‐specific lectin from Scylla serrata

Mercy¹,

Ravindranath

1993

European Journal of Biochemistry

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A sialic-acid-binding lectin with specificity for N-glycolylneuraminic acid (NeuGc) was purified from the hemolymph of the marine crab Scyllu serrutu by affinity chromatography using thyroglobulin-coupled agarose. The binding specificity of Scyllu lectin distinguishes it from other known sialic-acid-specific lectins found in Limulus polyphemus and Limux fluvus, which show a broader range of specificity for sialic acids. The molecular mass of the purified lectin is about 55 kDa.Under reducing conditions (SDWPAGE), it resolved into two subunits of 30 kDa and 25 kDa. NeuGc inhibited hemagglutination activity of the purified lectin at a concentration as low as 0.6 mM, whereas N-acetylneuraminic acid (NeuAc) even at a concentration of 100 mM, failed to inhibit hemagglutination. This finding was supported by potent inhibition of hemagglutination by bovine and porcine thyroglobulins, which contain a NeuGca2-6Gal as terminal component of oligosaccharide residues. Neither glycoproteins (glycophorin NN; porcine submaxillary mucin), which contain NeuAca2-3Gal/GalNAc and NeuAca2-6GalNAc, nor human acid glycoprotein, which contains NeuAca2-3/a2-6 Gal, or colominic acid, a sialopolymer with NeuAca2-8NeuAc, inhibited the lectin activity. The specificity of the lectin for NeuGc appears to account for the fact that it agglutinates rabbit and mice erythrocytes, but not human A, 0, AB, rat or chicken erythrocytes, which contain NeuAc. The inability of the lectin to agglutinate erythrocytes (horse) that prominently express NeuGc could be due to 0-acetylation of NeuGc. In support of this, bovine submaxillary mucin, which contains 0-acetylated NeuGc inhibited the hemagglutination of the lectin better after removal of 0-acetyl groups by base treatment. The unique specificity of Scyllu lectin is of diagnostic potential for human cancer tissues expressing NeuGc, since NeuGc is not found in normal human tissues.Invertebrate lectins may recognize a part of a sugar [l], a whole sugar [2], their glycosidic linkage [3-61, or a sequence of sugars [7, 81. Among invertebrates, arthropods and molluscs produce sialic-acid-specific lectins. Although crustaceans can not synthesize sialic acids [9, 101, they make sialic acid binding lectins as a defense against bacteria, which express a variety of sialoconjugates [l]. Plant lectins are not specific for sialic acids, and of the three sialic-acidbinding plant lectins, wheat germ agglutinin binds to GlcNAc [ l l ] and the other two recognize the glycosidic linkages of sialic acids [4-61. On the other hand, lectins purified from Limulus (horse-shoe crab) and Limux (slug) bind to NeuAc [l, 121, whereas Cancer (marine crab) lectin binds specifically to 0-acetylated sialic acids [l]. There are at least 18 different species of sialic acids in nature [13]. The type of sialic acid and the glycosidic linkages with the adjacent sugar in an oligosaccharide contribute to a remarkable diversity of Correspondence to Sister P. D. Mercy, Department of Zoology, Holy Cross College, Roche Nagar, Nagarcoil, Tamilnadu, I...

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Detection of Gangliosides as N‐Glycolylneuraminic Acid‐specific Tumor‐associated Hanganutziu‐Deicher Antigen in Human Retinoblastoma Cells

Cited by 57 publications

References 11 publications

Hypoxic Culture Induces Expression of Sialin, a Sialic Acid Transporter, and Cancer-Associated Gangliosides Containing Non–Human Sialic Acid on Human Cancer Cells

Hypoxic Culture Induces Expression of Sialin, a Sialic Acid Transporter, and Cancer-Associated Gangliosides Containing Non–Human Sialic Acid on Human Cancer Cells

Generation of Human Monoclonal Antibodies Against Ganglioside Antigens and Their Applications in the Diagnosis and Therapy of Cancer

Purification and characterization of N‐glycolylneuraminic‐acid‐specific lectin from Scylla serrata

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