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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 (Gal beta 4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Le(x), H type 2 and x(2) pentaosylceramides, the Le(y) and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (Gal alpha Gal beta 4Glc) 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.

As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were isolated and characterized with mass spectrometry and binding of carbohydrate-recognizing ligands, with a focus on complex compounds. The glycosphingolipid patterns of the human parathyroid and thyroid glands were very similar. The major acid glycosphingolipids were sulfatide and the gangliosides GM3, GD3, GD1a, GD1b, GT1b and Neu5Ac-neolactotetraosylceramide, and the major non-acid glycosphingolipids were globotriaosylceramide and globoside. We also found neolactotetra- and neolactohexaosylceramide, the x(2) glycosphingolipid, and complex glycosphingolipids with terminal blood group O and A determinants in both tissues. A glycosphingolipid with blood group Le(b) determinant was identified in the thyroid gland, and the parathyroid sample had a glycosphingolipid with terminal blood group B determinant. Immunohistochemistry demonstrated the expression of blood group A antigens in both the thyroid and parathyroid glands. A weak cytoplasmatic expression of the GD1a ganglioside was present in the thyroid, while the parathyroid gland had a strong GD1a expression on the cell surface. Thus, the glycosylation of human thyroid and parathyroid glands is more complex than previously appreciated. Our findings provide a platform for further studies of alterations of cell surface glycosphingolipids in thyroid and parathyroid cancers., De två första författarna delar förstaförfattarskapet.

Corynebacterium matruchotii may be key in tooth biofilm formation, but information about demographics, bacterial partners, and binding ligands is limited. The aims of this study were to explore C. matruchotii's demography by age and colonization site (plaque and saliva), in vitro bacterial-bacterial interactions in coaggregation and coadhesion assays, and glycolipids as potential binding ligands in thin-layer chromatogram binding assays. C. matruchotii prevalence increased from 3 months to 18 years old, with 90% and 100% prevalence in saliva and tooth biofilm, respectively. C. matruchotii aggregated in saliva in a dose-dependent manner but lacked the ability to bind to saliva-coated hydroxyapatite. In vivo, C. matruchotii abundance paralleled that of Actinomyces naeslundii, Capnocytophaga sp. HMT 326, Fusobacterium nucleatum subsp. polymorphum, and Tannerella sp. HMT 286. In vitro, C. matruchotii bound both planktonic and surface-bound A. naeslundii, Actinomyces odontolyticus, and F. nucleatum. In addition, C. matruchotii exhibited the ability to bind glycolipids isolated from human erythrocytes (blood group O), human granulocytes, rabbit intestine, human meconium, and rat intestine. Binding assays identified candidate carbohydrate ligands as isoglobotriaosylceramide, Gal alpha 3-isoglobotriaosylceramide, lactotriaosylceramide, lactotetraosylceramide, neolactotetraosylceramide, and neolactohexaosylceramide. Thus, C. matruchotii likely uses specific plaque bacteria to adhere to the biofilm and may interact with human tissues through carbohydrate interactions.

Ovarian carcinoma is a heterogeneous disease with distinct molecular and histological profiles, ranging from low grade atypia to highly aggressive tumors associated with a poor prognosis. In the present study, glycosphingolipids were isolated from human high-grade serous ovarian carcinoma, whereby the novel stem cell marker Sialyl-lactotetra (S-Lc4) was characterized in two out of three cases. The presence and level of S-Lc4 was further evaluated immunohistochemically in a cohort of patients with ovarian tumors ranging from benign lesions to high grade serous carcinoma (n = 478). Its expression was assessed in association with tumor grade, stage, histology, and survival. The data showed that S-Lc4 is most common and highly expressed in borderline type tumors and carcinomas with low levels of aggressiveness, such as mucinous, endometrioid, and low grade serous. Accordingly, S-Lc4-positivity was associated with better disease-free survival. The expression of S-Lc4 was seemingly associated with lineage continuity and could be traced from premalignant lesions to carcinoma, suggesting inheritance by a stem cell lineage that gives rise to generally indolent tumors.