Phenotypic changes induced by expression of beta-galactoside alpha2,6 sialyltransferase I in the human colon cancer cell line SW948.
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.
Chiricolo
Mariella
M
Dipartimento di Patologia Sperimentale, Università di Bologna, Via S. Giacomo 14, 40126 Bologna, Italy.
Malagolini
Nadia
N
Bonfiglioli
Silvia
S
Dall'Olio
Fabio
F
D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001212:Asialoglycoproteins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D010641:Phenotype; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism*; D014168:Transferrin / Q000031:analogs & derivatives / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D015703:Antigens, CD; D001212:Asialoglycoproteins; D019012:Integrin beta1; D009439:Neuraminidase; D012799:Sialyltransferases; D014168:Transferrin; C017031:asialotransferrins; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase