High-performance capillary electrophoretic analysis of hyaluronan and galactosaminoglycan-disaccharides in gastrointestinal carcinomas. Differential disaccharide composition as a possible tool-indicator for malignancies

The glycosaminoglycans (GAGs) have documented implications for the growth and progression of malignant tumors. Gastrointestinal carcinomas (gastric, colon, rectum and pancreatic) are the most frequent malignancies occurring in human. GAGs, isolated from the tissues after digestion with papain, were analyzed by high-performance capillary electrophoresis (HPCE) following treatment with chondroitinase ABC. The composition of GAGs in disaccharides derived from the various gastrointestinal carcinomas was compared with those of normal tissues. We report that human gastrointestinal carcinomas are characterized by increased concentrations of GAGs, which have quite different disaccharide composition which, in turn, is associated with marked increase of non-sulfated (Delta(di)-nonS) and 6-sulfated (Delta(di)-mono6S) Delta-disaccharides. Particularly, a 12-51-fold increase in Delta(di)-nonS and a 3-42-fold increase in Delta(di)-mono6S content characterize these carcinomas, while the 4-sulfated units (Delta(di)-mono4S) showed a lower increase, about 0.5-1.5-fold. Moreover, the quantitation of hyaluronan (HA)-derived Delta-disaccharides (Delta(di)-nonS(HA)) also revealed a marked increase (1-12-fold) in the malignant tissues. On the other hand, the content of the chondroitinase ABC-resistant GAGs showed a low decrease, about 0.2-0.7-fold. The high amounts of hyaluronan (HA) produced by these carcinomas and the ectopic production of chondroitin sulphate (CS) proteoglycans, in which (Delta(di)-nonS) and (Delta(di)-mono6S) predominated, suggest a close relation between the content of these GAGs and the malignant phenotype, the metastatic ability and the survival time.