Incomplete synthesis of the Sd/Cad blood group carbohydrate in gastrointestinal cancer

Cancer-associated changes in cell surface carbohydrates, including incomplete synthesis of normal carbohydrate epitopes, strongly affect malignant and metastatic potential. Here, we report that compensating for the cancer-associated loss of a single glycosyltransferase, β1,4N-acetylgalactosaminyltransferese T2, dramatically decreased cell surface expression of both E-selectin ligands (sialyl Lewis^x and sialyl Lewis^a). This modification was associated with elevated expression of the Sd^a carbohydrate determinant, which is expressed in normal gastrointestinal mucosa and is strikingly downregulated in cancer tissues. Loss of E-selectin ligands resulted in decreased adhesion of cancer cells to activated human endothelial cells in vitro and eventually suppressed metastatic potential in vivo.