Expression of β-galactoside α2,6-sialyltransferase does not alter the susceptibility of human colon cancer cells to NK-mediated cell lysis

• Published in: Glycobiology (Oxford) 1997-06, Vol.7 (4), p.507-513
• Main Authors: Dall'Olio, Fabio, Mariani, Erminia, Tarozzi, Andrea, Meneghetti, Alessandra, Chiricolo, Mariella, Lau, Joseph T. Y., Facchini, Andrea
• Format: Article
• Language: English
• Subjects: colon cancer cells; natural killer cells; sialyltransferases
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/7.4.507

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 β-ga-lactoside α2,6-sialyltransferase (EC 2.4.99.1, α2,6ST), which catalyzes the addition of sialic acid in α2,6-linkage to Galβ1,4GlcNAc (N-acetyllactosamine) sequences of glycoprotein N-linked chains. The resulting increased level of membrane α2,6-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 α2,6ST cDNA. Stable transfectants expressed different levels of α2,6ST activity, were reactive with the Sambucus nigra lectin, specific for α2,6-linked sialic acid, and, compared with control transfectants, showed a remarkable decrease in the number of unsubstituted Galβ1,4GlcNAc 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 α2,6-linked to N-linked chains of target cell glycoproteins does not play a major role in recognition of the target by human NK cells.