Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

International Journal of Molecular Sciences

Susann Teneberg¹  Chunsheng Jin¹  Karin Säljö²  Olov Norlén³  Anders Thornell⁴ 

[1] Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, S-40530 Gothenburg, Sweden;Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden;Department of Surgical Sciences, Uppsala University, S-75185 Uppsala, Sweden;Region Västra Götaland, Sahlgrenska University Hospital, S-41345 Gothenburg, Sweden;

关键词: human medullary thyroid cancer marker;    glycosphingolipid characterization;    mass spectrometry;    Lewis y antigen;    Forssman antigen;   

DOI  :  10.3390/ijms221910463

来源: DOAJ

【 摘 要 】

Medullary thyroid carcinoma (MTC) accounts for only 1–2% of thyroid cancers; however, metastatic MTC is a mortal disease with no cure. In this study, glycosphingolipids were isolated from human MTCs and characterized by mass spectrometry and binding of carbohydrate recognizing ligands. The tissue distribution of selected compounds was investigated by immunohistochemistry. The amount of acid glycosphingolipids in the MTCs was higher than in the normal thyroid glands. The major acid glycosphingolipid was the GD3 ganglioside. Sulfatide and the gangliosides GM3 and GD1a were also present. The majority of the complex non-acid glycosphingolipids had type 2 (Galβ4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Le^x, H type 2 and x₂ pentaosylceramides, the Le^y and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (GalαGalβ4Glc) core, i.e., globotriaosylceramide, globotetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Immunohistochemistry demonstrated an extensive expression av Le^y in the MTC cells and also a variable intensity and prevalence of Globo H and Le^x. One individual with multiple endocrine neoplasia type 2B expressed the Forssman determinant, which is rarely found in humans. This study of human MTC glycosphingolipids identifies glycans that could serve as potential tumor-specific markers.

【 授权许可】

Unknown