Reduced sulfation of chondroitin sulfate in thyroglobulin derived from human papillary thyroid carcinomas.
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.
Emoto
Naoya
N
Department of Medicine, Nippon Medical School Chiba-Hokusoh Hospital, Inba-gun, Chiba, 270-1694, Japan. n-emoto@nms.ac.jp
Kunii
Yo Kidokoro
YK
Ashizawa
Masayo
M
Oikawa
Shinichi
S
Shimizu
Kazuo
K
Shimonaka
Motoyuki
M
Toyoda
Akiko
A
Toyoda
Hidenao
H
D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
D004187:Disaccharides; D002809:Chondroitin Sulfates; D013954:Thyroglobulin