Abstract
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 Lex, H type 2 and x2 pentaosylceramides, the Ley 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 Ley in the MTC cells and also a variable intensity and prevalence of Globo H and Lex. 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.
Highlights
IntroductionMedullary thyroid carcinoma (MTC) accounts for only 1–2% of thyroid cancers [1]
Medullary thyroid carcinoma (MTC) accounts for only 1–2% of thyroid cancers [1].Unlike the rather common follicular cell-derived thyroid cancers, papillary thyroid cancer and follicular thyroid cancer, MTC originates from parafollicular C-cells [2]
Total acid and non-acid glycosphingolipid fractions were isolated from pooled human medullary carcinomas of the thyroid by standard procedures [13]
Summary
Medullary thyroid carcinoma (MTC) accounts for only 1–2% of thyroid cancers [1]. Unlike the rather common follicular cell-derived thyroid cancers, papillary thyroid cancer and follicular thyroid cancer, MTC originates from parafollicular C-cells [2]. Radioiodine imaging and treatment, successfully used for iodine-avid follicular cell-derived cancers, is not applicable to MTC. MTC has a high propensity to metastasize both to lymph nodes and parenchymal organs rendering the disease difficult to cure with surgery, especially since MTC metastases can be difficult to image with currently available radiological methods. Chemotherapy has little effect in MTC, and available oncological treatments such as tyrosine kinase inhibitors offers partial response in less than 50% of all patients [3,4]. A search for novel druggable targets for MTC is warranted
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