Beta-galactoside alpha2,6 sialyltransferase (
ST6Gal.I), the
enzyme which adds
sialic acid in alpha2,6-linkage on lactosaminic termini of
glycoproteins, is frequently overexpressed in
cancer, but its relationship with
malignancy remains unclear. In this study, we have investigated the phenotypic changes induced by the expression of alpha2,6-sialylated lactosaminic chains in the human
colon cancer cell line SW948 which was originally devoid of
ST6Gal.I. Clones derived from transfection with the
ST6Gal.I cDNA were compared with untransfected cells and mock transfectants. The ST6Gal.I-expressing clones show (1) increased adherence to
fibronectin and
collagen IV but not to
hyaluronic acid. Treatment with Clostridium perfrigens
neuraminidase reduces the binding to
fibronectin and
collagen IV of ST6Gal.I-expressing cells but not that of ST6Gal.I-negative cells; (2) accumulation and more focal distribution of beta1
integrins on the cell surface; (3) different distribution of actin fibers; (4) flatter morphology and reduced tendency to multilayer growth; (5) improved ability to heal a scratch
wound; (6) reduced ability to grow at the subcutaneous site of injection in nude mice. Our data suggest that the presence of alpha2,6-linked
sialic acid on membrane
glycoconjugates increases the binding to extracellular matrix components, resulting in a membrane stabilization of beta1
integrins, further strengthening the binding. This mechanism can provide a basis for the flatter morphology and the reduced tendency to multilayer growth, resulting in a more ordered tissue organization. These data indicate that in the cell line SW948, the effect of
ST6Gal.I expression is consistent with the attenuation of the neoplastic phenotype.