Expression of beta-galactoside alpha 2,6-sialyltransferase does not alter the susceptibility of human colon cancer cells to NK-mediated cell lysis.
The extent of processing of N-linked oligosaccharides and the sialylation of the target cell membranes has been positively correlated with resistance to lysis mediated by NK cells, but a conclusive evidence has never been reached. Colon cancer tissues express an increased activity of beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, alpha 2,6ST), which catalyzed the addition of sialic acid in alpha 2,6-linkage to Gal beta 1,4GlcNAc (N-acetyllactosamine) sequences of glycoprotein N-linked chains. The resulting increased level of membrane alpha 2,6-sialylation appears to be related with a more invasive behavior of cancer cells. This phenomenon may depend on a decreased sensitivity of colon cancer cells to NK cells. To obtain conclusive evidence on the role played by sialylation of N-linked chains in determining the target cell susceptibility to NK-mediated lysis, human colon cancer cell lines not expressing sialyltransferases acting on N-linked chains were transfected with a rat alpha 2,6ST cDNA. Stable transfectants expressed different levels of alpha 2,6ST activity, were reactive with the Sambucus nigra lectin, specific for alpha 2,6-linked sialic acid, and compared with control transfectants, showed a remarkable decrease in the number of unsubstituted Gal beta 1,4GlcNAc terminal sequences. The NK susceptibility of these clones was found to be identical to that of control transfectants, either when unstimulated- or IL-2-stimulated lymphocytes were used as effectors. Neuraminidase treatment of target cells does not result in significant changes to NK susceptibility. Our data demonstrate that sialic acid alpha 2,6-linked to N-linked chains of target cell glycoproteins does not play a major role in recognition of the target by human NK cells.
Dall'Olio
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Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
Mariani
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E
Tarozzi
A
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Meneghetti
A
A
Chiricolo
M
M
Lau
J T
JT
Facchini
A
A
D000606:Amino Sugars / Q000378:metabolism; D002236:Carbohydrate Conformation; D003110:Colonic Neoplasms / Q000276:immunology*; D015870:Gene Expression; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D000606:Amino Sugars; D015395:Histocompatibility Antigens Class I; C000458:N-acetyllactosamine; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase