Human colon adenocarcinoma is associated with specific post-translational modifications of versican and decorin.
In this study, the amounts and the fine structural characteristics of versican and decorin present in human colon adenocarcinomas (HCC) were investigated and compared with those in human normal colon (HNC). HCC is characterized by significant increase in the amounts of versican and decorin (13- and 8-fold in terms of protein, respectively). These two proteoglycans (PGs) were the predominant in HCC (86% of total uronic acid). In HNC, versican and decorin contained both chondroitin sulfate/dermatan sulfate chains (CS/DS), with DS to be the predominant one (90-93%). The molecular sizes (M(r)s) estimated for DS and CS chains were 25-28 and 21-28 kDa, respectively. In CS/DS chains isolated from both versican and decorin, 4-sulfated disaccharides accounted for 79-86% of total disaccharide units, respectively, whereas lower amounts of 6- and non-sulfated units were also recorded. In contrast, the tumor-associated versican and decorin were of smaller hydrodynamic size with lower glycosaminoglycan (GAG) content per PG molecule as compared with those found in HNC. In HCC, both PGs contained mainly CS chains (up to 86%) and the M(r)s of CS and DS chains were also found to be of smaller size (12 and 16 kDa, respectively). The sulfation patterns of CS/DS chains from both PGs were also significantly different. They were composed mainly of 6-sulfated disaccharides (63-70%), whereas 4-sulfated units accounted for 23-31%. A significant increase in the proportion of non-sulfated disaccharides was also recorded. These findings indicate that the colon adenocarcinoma is characterized by a remarkable increase in the concentration of versican and decorin. Furthermore, these PGs are significantly modified at the post-translational level, i.e. the type, length and the sulfation pattern of their GAG chains. These specific structural alterations of versican and decorin may influence the biology of cancer cells in HCC.
Theocharis
Achilleas D
AD
Department of Chemistry, Section of Organic Chemistry, Biochemistry and Natural Products, Laboratory of Biochemistry, University of Patras, 261 10 Patras, Greece.
D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002850:Chromatography, Gel; D003082:Colectomy; D003110:Colonic Neoplasms / Q000378:metabolism*; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D015151:Immunoblotting; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; C508322:VCAN protein, human; D053675:Versicans