Incomplete synthesis of the Sda/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, beta1,4N-acetylgalactosaminyltransferase 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.
Dohi
Taeko
T
Department of Gastroenterology, Research Institute, International Medical Center of Japan, Toyama 1-21-1, Shinjuku, Tokyo 162-8655, Japan. dohi@ri.imcj.go.jp
Kawamura
Yuki I
YI
D000818:Animals; D001789:Blood Group Antigens / Q000096:biosynthesis*; D019040:E-Selectin / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis*; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D010295:Parietal Cells, Gastric / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D001789:Blood Group Antigens; D019040:E-Selectin; D006017:Glycolipids; D007983:Lewis Blood Group Antigens; D008024:Ligands; D012333:RNA, Messenger; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase