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

摘要

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, beta 1,4N-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. (c) 2007 Elsevier B.V. All rights reserved.