Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

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.

Galactia lindenii lectin type-II. Proposal of its potential use in diagnostic tools

“…H-type-II glycotope Fucosylation is altered in in amed and cancer tissues [75,76,90]. Glycoconjugates containing α-Fuc participate in diverse interactions between cells and ECM [105][106][107], and the change in their expression correlates with tumor growth, invasion, and metastasis [95,[107][108][109][110][111][112][113]. The aberrant fucosylation is mainly attributed to upregulation of fucosyltransferases (FUTs) and downregulation of α-L-fucosidases (FUCAs), promoting in ammatory conditions and malignancy [19-21, 105, 108, 113-115].…”

“…d) Globo-H ceramide recognized in tissue microarrays [123]. In thyroid cancer, the H-type-II glycotope has been more readily and frequently detected in PTC compared to follicular adenomas, FTC and ATC [77,95,97,98,101,120,121]; meanwhile, it also has been found in the non-acid glycosphingolipid fraction isolated from human neuroendocrine medullary thyroid carcinoma (MTC), as determined by mass spectrometry [112].…”

A novel and highly specific Forssman antigen-binding protein from sheep polyomavirus

“…Other reports of healthy human FA+ tissues are scarce, and human sera often contain natural anti-FA antibodies [9][10][11] . More frequently, Forssman antigenicity was described in cancerogenesis and a few other diseases of humans [12][13][14][15][16][17][18][19][20][21] . Yet, both the genetics and the precise role of FA expression in disease remain poorly understood.…”