Altered glycosylation of proteins produced by malignant cells, and application for the diagnosis and immunotherapy of tumours.
Most secretory and membrane-bound proteins produced by mammalian cells contain covalently linked sugar chains. Alterations of the sugar chain structures of glycoproteins have been found to occur in various tumours. Because the sugar chains of glycoproteins are essential for the maintenance of the ordered social behaviour of differentiated cells in multicellular organisms, alterations to the sugar chains are the molecular basis of abnormal social behaviours in tumour cells, such as invasion into the surrounding tissues and metastasis. In this review, the structure and enzymatic basis of typical alterations of the N-linked sugar chains, which are found in various tumours, are introduced. These data are useful for devising diagnostic methods and immunotherapies for the clinical treatment of tumours. Three beta-N-acetylglucosaminyltransferases, GnT-III, -IV and -V, play roles in the structural alteration of the complex-type sugar chains in various tumours. In addition, transcriptional changes in various glycosyltransferases, together with the transporters of sugar nucleotides and sulfate, which are responsible for the formation of the outer chain moieties of complex-type sugar chains, are the keys to inducing the alterations.
Kobata
Akira
A
TheNoguchi Institute, Tokyo, Japan. akobata@mx5.ttcn.ne.jp
Amano
Junko
J
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007167:Immunotherapy; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D015295:Antigens, Tumor-Associated, Carbohydrate; D006023:Glycoproteins; D017351:N-Acetylglucosaminyltransferases; C037649:N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase