N-linked oligosaccharide processing and tumor cell biology.
A variety of alterations in carbohydrate structure have been observed in cancer cells. Most are carbohydrate sequences normally found in other adult or embryonic tissues and their expression in cancer cells appears to reflect a change in the differentiated state of transformed cells. The expression of branched and sialylated complex-type N-linked oligosaccharides in malignant tumor cells appears to be directly associated with metastatic potential. Inhibition of N-linked oligosaccharide processing in malignant cells is associated with increased susceptibility to natural immunity, increased cell adhesion to extracellular matrix and decreased tumor cell invasion in vitro. There is also growing evidence that branched complex-type oligosaccharides participate in organ retention of blood-borne tumor cells by acting as ligands for endothelial cell lectins. These observations suggest that inhibitors of N-linked oligosaccharide processing may be useful anti-cancer agents.
Dennis
J W
JW
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
D000818:Animals; D014408:Biomarkers, Tumor; D002240:Carbohydrate Sequence; D002448:Cell Adhesion; D006031:Glycosylation; D006801:Humans; D007212:Indolizines / Q000494:pharmacology / Q000627:therapeutic use; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009369:Neoplasms / Q000378:metabolism*; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D017026:Swainsonine / Q000494:pharmacology / Q000627:therapeutic use; D054836:Indolizidines
D014408:Biomarkers, Tumor; D007212:Indolizines; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D017026:Swainsonine; C037806:castanospermine; D054836:Indolizidines