A role of α2,6-linked sialic acid in the development of an invasive phenotype in colon cancer has been suggested by several observations but never conclusively demonstrated. An experimental model to clarify this issue was established by the creation and characterization of a bank of cell lines that differ mainly, if not exclusively, in the degree of α2,6-sialylation. Human colon cancer cell lines SW48 and SW948, normally unable to elaborate the α2,6-sialyl linkage, were transfected with the β-galactoside α2,6-sialyltransferase (α2,6ST) cDNA driven by the cytomegaloviral promoter and screened for cell surface α2,6-sialylated sugar chains using fluorescein isothiocyanate-conjugated Sambucus nigra agglutinin (SNA-FITC). A panel of SNA-FITC-positive clones was established that expresses α2,6ST activity to varying degrees. Only the SNA-FITC-positive recombinants express the 1.2 Kb mRNA predicted to be generated from the transfected sequence. No 4.3-4.7 Kb transcripts that are indicative of transcription from the native α2,6St gene were detected.Copyright 1995, 1999 Academic Press, Inc.