Altered glycosylation of proteins produced by malignant cells, and application for the diagnosis and immunotherapyof tumours

Most secretory and membrane-bound proteins produced by mammalian cells containcovalently linked sugar chains. Alterations of the sugar chain structuresof glycoproteins have been found to occur in various tumours. Becausethe sugar chains of glycoproteins are essential for the maintenanceof the ordered social behaviour of differentiated cells in multicellularorganisms, alterations to the sugar chains are the molecular basisof abnormal social behaviours in tumour cells, such as invasioninto the surrounding tissues and metastasis. In this review, the structureand enzymatic basis of typical alterations of the N-linkedsugar chains, which are found in various tumours, are introduced.These data are useful for devising diagnostic methods and immunotherapiesfor the clinical treatment of tumours. Three beta-N-acetylglucosaminyltransferases,GnT-III, -IV and -V, play roles in the structural alteration of thecomplex-type sugar chains in various tumours. In addition, transcriptionalchanges in various glycosyltransferases, together with the transportersof sugar nucleotides and sulfate, which are responsible for theformation of the outer chain moieties of complex-type sugar chains,are the keys to inducing the alterations.