Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and -81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen.

Hirohashi, Setsuo; Clausen, Henrik; Yamada, Tesshi; Shimosato, Yukío; Hakomori, Sen‐itiroh

doi:10.1073/pnas.82.20.7039

Cited by 162 publications

(88 citation statements)

References 25 publications

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“…O-linked glycoepitopes present in mucin-type structures include (i) ABH and Lewis blood group antigens; (ii) tumorassociated antigens T, Tn (77,78), and sialyl-Tn (79, 80); (iii) E-selectin epitopes sialyl-Le x (32) and sialyl-Le a (81,82) 30). The ''myeloglycan'' epitope (see Table 1 for structure) found originally in GSLs (35,36) may well be present in O-linked form in PSGL-1 and other mucin-type glycoproteins.…”

Section: Type 2 Glycosynapse: O-linked Mucin-type Adhesion Epitopes Omentioning

confidence: 99%

The glycosynapse

Hakomori

2002

Proc. Natl. Acad. Sci. U.S.A.

475

217

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Physically distinguishable microdomains associated with various functional membrane proteins are one of the major current topics in cell biology. Glycosphingolipids present in such microdomains have been used as “markers;” however, the functional role of glycosyl epitopes in microdomains has received little attention. In this review, I have tried to summarize the evidence that glycosyl epitopes in microdomains mediate cell adhesion and signal transduction events that affect cellular phenotypes. Molecular assemblies that perform such functions are hereby termed “glycosynapse” in analogy to “immunological synapse,” the membrane assembly of immunocyte adhesion and signaling. Three types of glycosynapses are so far distinguishable: (i) Glycosphingolipids organized with cytoplasmic signal transducers and proteolipid tetraspanin with or without growth factor receptors; (ii) transmembrane mucin-type glycoproteins with clustered O-linked glycoepitopes for cell adhesion and associated signal transducers at lipid domain; and (iii) N-glycosylated transmembrane adhesion receptors complexed with tetraspanin and gangliosides, as typically seen with the integrin–tetraspanin–ganglioside complex. The possibility is discussed that glycosynapses give rise to a high degree of diversity and complexity of phenotypes

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Section: Type 2 Glycosynapse: O-linked Mucin-type Adhesion Epitopes Omentioning

confidence: 99%

The glycosynapse

Hakomori

2002

Proc. Natl. Acad. Sci. U.S.A.

475

217

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“…In addition to GSLs indicated to be associated with CSCs in this study, the following were found to be highly expressed in human cancer but either absent or present in negligible amounts in normal cells/tissues: (i) blood group A-like antigens expressed in tumor cells of blood group O or B patients [the structure is GalNAcα1-O-Ser/Thr, termed Tn (63)(64)(65); (ii) sialyl 2-6Tn antigen [i.e., NeuAcα2-6GalNAcα1-O-Ser/Thr (66)]; and (iii) extended type-I antigen [i.e., Le a on Le a (67) or Le b on Le a (68,69)]. Whether these glycan structures are somehow associated with CSCs is an interesting point for future studies.…”

Section: Discussionmentioning

confidence: 99%

Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

Liang

Ding

Levery

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

147

120

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Previous studies demonstrated that certain glycosphingolipids (GSLs) are involved in various cell functions, such as cell growth and motility. Recent studies showed changes in GSL expression during differentiation of human embryonic stem cells; however, little is known about expression profiles of GSLs in cancer stem cells (CSCs). CSCs are a small subpopulation in cancer and are proposed as cancer-initiating cells, have been shown to be resistant to numerous chemotherapies, and may cause cancer recurrence. Here, we analyzed GSLs expressed in human breast CSCs by applying a CSC model induced through epithelial-mesenchymal transition, using mass spectrometry, TLC immunostaining, and cell staining. We found that (i) Fuc-(n)Lc4Cer and Gb3Cer were drastically reduced in CSCs, whereas GD2, GD3, GM2, and GD1a were greatly increased in CSCs; (ii) among various glycosyltransferases tested, mRNA levels for ST3GAL5, B4GALNT1, ST8SIA1, and ST3GAL2 were increased in CSCs, which could explain the increased expression of GD3, GD2, GM2, and GD1a in CSCs; (iii) the majority of GD2+ cells and GD3+ cells were detected in the CD44 hi /CD24 lo cell population; and (iv) knockdown of ST8SIA1 and B4GALNT1 significantly reduced the expression of GD2 and GD3 and caused a phenotype change from CSC to a non-CSC, which was detected by reduced mammosphere formation and cell motility. Our results provide insight into GSL profiles in human breast CSCs, indicate a functional role of GD2 and GD3 in CSCs, and suggest a possible novel approach in targeting human breast CSCs to interfere with cancer recurrence.

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“…At present, it is known that mAb B72.3 identifies a sialyl-Tn epitope, and CC49 has been claimed to react with other oligosaccharides; this study demonstrates that 83D4 identifies a novel epitope and that sugar moieties take part in it. A number of tumour-associated glycoprotein carbohydrate epitopes have been detected by mAb, and some of them have been characterised, including antigen reactive with the mAb 19-9 directed to a sialyl-Lea carbohydrate chain carried on a gastrointestinal-cancer-associated mucin (Magnani et al, 1983), and the Tn antigen identified by mAb NCC-LU-35 and NCC-LU-81 raised against squamous lung carcinomas (Hirohashi et al, 1985). Aberrant glycosylation of glycoprotein antigens is a common phenomenon in human cancers (reviewed in Hakomori, 1989).…”

Section: Discussionmentioning

confidence: 99%

Purification and characterisation of a breast-cancer-associated glycoprotein not expressed in normal breast and identified by monoclonal antibody 83D4

Pancino

Osinaga²,

Charpin³

et al. 1991

Br J Cancer

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The purpose of the present study was to purify and characterise the antigen identified by mAb 83D4. The antigen was isolated from different sources, and purified antigen was analysed by biochemical and immunological methods. Moreover, the reactivity of mAb HMFG-1 (TaylorPapadimitriou et al., 1981) defining the PEM antigen and of mAb B72.3 and CC49 (Muraro et al., 1988), defining the TAG-72 antigen, with the 83D4 purified antigen was investigated. Materials and methods mAbIgM mAb 83D4 was generated by immunisation of Balb/c mice with cell suspensions from formalin-fixed paraffinembedded sections of an invasive human breast carcinoma as described in detail elsewhere (Pancino et al., 1990a). The antibody was purified from ascitic fluid by dialysis against demineralised water (Garcia-Gonzales et al., 1988). Precipitated antibody was resuspended in 0.1 M Tris-HCI pH 8, 1 M NaCl and dialysed against the appropriate buffer.Control antibodies produced in our laboratory were BIN, an IgM reactive with a nuclear protein; CA4, an IgM raised to a human milk cell glycoprotein (Pancino et al., 1991) and 1BE12, an IgM mAb against a breast-cancer-associated glycoprotein (Pancino et al., 1990b). Culture supernatant containing mAb HMFG-1 (Taylor-Papadimitriou et al.,

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Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and -81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen.

Cited by 162 publications

References 25 publications

The glycosynapse

The glycosynapse

Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

Purification and characterisation of a breast-cancer-associated glycoprotein not expressed in normal breast and identified by monoclonal antibody 83D4

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