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 sialylat ion of the target cell membranes has been positively correlated with r esistance to lysis mediated by NK cells, but a conclusive evidence has never been reached, Colon cancer tissues express an increased activit y of beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, alpha 2,6ST), which catalyzes the addition of sialic acid in alpha 2,6-linka ge to Gal beta 1,4GlcNAc (N-acetyllaetosamine) sequences of glycoprote in N-linked chains. The resulting increased level of membrane alpha 2, 6-sialylation appears to be related with a more invasive behavior of c ancer cells, This phenomenon may depend on a decreased sensitivity of colon cancer cells to NK cells, To obtain conclusive evidence on the r ole played by sialylation of N-linked chains in determining the target cell susceptibility to NK-mediated lysis, human colon cancer cell lin es not expressing sialyltransferases acting on N-linked chains were tr ansfected with a rat alpha 2,6ST cDNA, Stable transfectants expressed different levels of alpha 2,6ST activity, were reactive with the Sambu cus nigra lectin, specific for alpha 2,6-linked sialic acid, and, comp ared with control transfectants, showed a remarkable decrease in the n umber of unsubstituted Gal beta 1,4GlcNAc terminal sequences, The NK s usceptibility of these clones was found to be identical to that of con trol transfectants, either when unstimulated- or IL-2-stimulated lymph ocytes were used as effecters, 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 t arget cell glycoproteins does not play a major role in recognition of the target by human NK cells.