chondroitin-sulfates and Thyroid-Neoplasms

The presence of a chondroitin sulfate (CS) chain on human thyroglobulin (Tg) distinguishes it from Tg of other species; the role played by this chain in normal thyroid function is unclear. In the present study, we determined the structure of the CS oligosaccharides in human thyroid-derived Tg. Q-Sepharose anion exchange column chromatography of thyroid extracts indicated that the negative charge of human Tg was primarily due to the presence of the CS chain. Interestingly, the Tg of papillary carcinomas was less negatively charged, suggesting that its CS side chain was less sulfated. Structural analysis of the CS in Tg revealed that its most abundant disaccharide is the DeltaDi-0S unit (50.2 +/- 18.3%), which is not sulfated. The DeltaDi-0S, DeltaDi-6S (31.7 +/- 13.7%) and DeltaDi-diSD (12.8 +/- 4.3%) units comprise more than 90% of the disaccharides in normal Tg. However, the DeltaDi-6S (0.0-21.2%) and DeltaDi-diSD (0.0-7.7%) units were significantly reduced in Tg extracted from papillary thyroid carcinomas, whereas DeltaDi-0S (86.0 +/- 21.3%) was increased. These results suggest that the Tg in papillary carcinomas has a less sulfated CS side chain and, by virtue of that fact, is less negatively charged. What role this change in carcinoma cells has in their transformation and spread remains to be determined.

Topics: Carcinoma, Papillary; Chondroitin Sulfates; Disaccharides; Humans; Immunoblotting; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms

Human thyroglobulin (TG) is one of a growing number of glycoproteins that are known to contain sulfate. Among these TG is unusual because it contains sulfate on both its asparagine-linked complex carbohydrate units and its single chondroitin 6-SO4 unit. We incubated tissue fragments prepared from normal and neoplastic thyroid tissue with [35S]sulfate to study the incorporation of sulfate into these two types of carbohydrate acceptor sites. Incubation conditions (0.1 mM sulfate for 16 h) were selected that maintained linear incorporation of [35S]sulfate and retention of more than 90% of iodinated TG in the tissue. Enzyme susceptibility was used to determine incorporation into the complex carbohydrate units (endoglycosidase-F) and the chondroitin 6-SO4 unit (chondroitin ABC lyase). In a representative experiment, 29.8% of the incorporated sulfate was found in the chondroitin 6-SO4 unit during the first hour of incubation. This increased progressively to 72.5% in the chondroitin unit during the incubation period from 8-16 h. A reciprocal decrease occurred in the proportion of sulfate incorporated into the complex carbohydrate units. TG released into the medium and retained in the tissue had the same ratio of sulfate in the two types of carbohydrate units. Neoplastic thyroid tissue incorporated more [35S]sulfate into TG than normal thyroid tissue from the same patient. Neoplastic and normal tissue differed further in the ratios of sulfate incorporated into the two types of carbohydrate units. We conclude that the incorporation of sulfate into the two types of sulfate-containing carbohydrate units of TG does not occur in a fixed ratio and that this differential incorporation of sulfate does not appear to be related to its release from the tissue.

Topics: Carbohydrate Metabolism; Chondroitin; Chondroitin Lyases; Chondroitin Sulfates; Glycoside Hydrolases; Humans; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; Sulfates; Thyroglobulin; Thyroid Neoplasms