Asparagine-linked oligosaccharides associated with metastatic cancer.
Malignant transformation and tumor progression are often accompanied by structural changes in the carbohydrate components of glycoproteins and glycolipids. Studies with tumor cell glycosylation mutants and specific inhibitors of glycosylation indicate that expression of sialylated and beta (1-6) branched asparagine (Asn)-linked oligosaccharides are required for tumor cell invasion and metastasis. The initiation of the beta (1-6) antenna appears to be oncodevelopmentally regulated and may be associated with the aberrant expression of blood group and embryonic carbohydrate sequences in Asn-linked oligosaccharides of tumors. Although the function of these oligosaccharides in the metastatic process remains unclear, there is some evidence that expression of these structures on certain cell-surface glycoproteins may reduce tumor cell adhesion to extracellular matrix. These observations suggest that low-toxicity drugs that inhibit the biosynthesis of these structures may be useful in the treatment of metastatic cancers.
Dennis
J W
JW
Division of Cancer and Cell Biology, Mount Sinai Hospital Research Institute, Ontario, Canada.
Laferté
S
S
Yagel
S
S
Breitman
M L
ML
D000818:Animals; D001216:Asparagine / Q000378:metabolism*; D002240:Carbohydrate Sequence; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009844:Oligosaccharides / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D009844:Oligosaccharides; D001216:Asparagine