Glycosphingolipids in human abdominal leiomyosarcoma and liposarcoma

Retroperitoneal sarcomas (liposarcomas and leiomyosarcomas) are rare and highly malignant mesenchymal tumors with poor prognosis, since they often reach a large size before detection, due to their anatomical location. Thus, development of new tumor biomarkers for early detection of these cancers is urgently needed. In search for potential sarcoma biomarkers, this study examined the glycosphingolipid profiles of one leiomyosarcoma and one liposarcoma by mass spectrometry, enzymatic hydrolysis, and by binding of carbohydrate-recognizing ligands. Detailed mass spectrometry analyses of oligosaccharides released from the glycosphingolipids showed that the liposarcoma had a number of glycosphingolipids previously found in many human tissues (the gangliosides GM3, GD3, GM2, GD1a, sialylneolactotetra- and hexaosylceramide, globo- and lactotriaosylceramide, globo- and lactotetraosylceramide, x₂ pentaosylceramide, H type 2 penta- and heptaosylceramide, neolactotetra- and heptaosylceramide). The leiomyosarcoma had a more complex glycosphingolipid composition, and in addition to the compounds listed above, it contained sialyl-lactotetraosylceramide, sialyl-globotetraosylceramide, globopentaosylceramide/SSEA-3, sialyl-globopentaosylceramide/SSEA-4, and disialyl-globopentaosylceramide. The expression of sialyl-globopentaosylceramide/SSEA-4 in leiomyosarcoma was confirmed by immunohistochemistry. Thus, the leiomyosarcoma had several glycosphingolipids also found in human pluripotent stem cells. These insights may have important clinical implications for the development of novel diagnostic and therapeutic strategies for sarcomas.