Synthesis of O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D- glucopyranose and two related trisaccharides containing the “lacto-N-biose II” unit

Thomas, Rexford L.; Dubey, Rajeev K.; Abbas, Saeed A.; Matta, Khushi L.

doi:10.1016/0008-6215(87)80251-3

Cited by 8 publications

(1 citation statement)

References 14 publications

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“…GalPl3GalNAca-Np was obtained from Toronto Research Chemicals. The following compounds were synthesized as previously described : GlcNAcPl-6(GalPl -3)GalNAca-Bzl [21], GlcNAc~l-6(GlcNAc~1-3Ga1~1-3)GalNAca-Bzl [22], GlcNAcPl-6 GalNAca-Bzl [23], GlcNAcPl-3 GalP1-4 GlcNAc [24], 2-0-Me-GalP1-3 GlcNAcP-Bzl [25] and 2-0-Me-GalPl-4 GlcNAcP-Bzl [26].…”

Section: Substrates and Standardsmentioning

confidence: 99%

O‐glycan biosynthesis in human colorectal adenoma cells during progression to cancer

Vavasseur

Dole

Yang

et al. 1994

European Journal of Biochemistry

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129

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A human colonic adenoma cell line PCIAA derived from a familial polyposis coli patient was passaged in culture to form an intermediate premalignant clonogenic variant AA/Cl and, upon treatment with differentiating and carcinogenic agents, a cell line AA/Cl/SB10 which is tumourigenic in nude mice. These three mucin-secreting cell lines have been used as a model to study the changes in 0-glycan biosynthesis during the progression to cancer. Several glycosyltransferases involved in the synthesis, elongation and termination of the common 0-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. 0-glycan biosynthesis in the original PCIAA cell line was closest to the normal human colonic phenotype, since all four common mucin 0-glycan cores and their extended structures could be synthesized; core 3 fl-GlcNAc-transferase and a6-sialyltransferase acting on GalNAc-mucin were still detectable and core 2 P6-GlcNAc-transferase activity was accompanied by core 4 and I P6-GlcNAc-transferase activities. During progression towards adenocarcinoma, the expression of a6-sialyltransferase, core 3 fl-GlcNAc-transferase, core 4 and I P6-GlcNAc-transferases were turned off. Using monoclonal antibodies, Tn antigen, sialylTn antigen, 0-acetyl-sialomucin and sialyl-Lea determinants were not detected in secreted or cellular mucin isolated from any of the cell lines. The exposure of MUCl epitopes was seen in the malignant line, whereas sialyl-Le" determinants were found only in the premalignant PC/AA line. Sulfotransferase activities using core 1 substrate, GalPl-3GalNAca-benzy1, were high in PCIAA 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.The glycosylation of secreted and membrane-bound mucins is sensitive to cellular differentiation and transformation. It has previously been shown that glycosyltransferases assembling the 0-glycan chains of mucins are significantly changed in human colon cancer tissue compared to normal tissue [l]. Since there is great variability between individuals, and tissue represents a mixture of different cell types, we have now chosen cultured cell lines to study the assembly of mucin carbohydrate chains during tumour progression.Familial polyposis coli is an inherited disease in which individuals will develop colon carcinoma at a much earlier age than expected normally. Generally, most colonic carci- Np, p-nitrophenyl. noma are thought to originate from polyps and human coloni...

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