Characterization of glycosphingolipids from gastrointestinal stromal tumours

Licínia Santos,Karin Säljö,Olov Norlén,Taťána Gazárková,Chunsheng Jin,Anders Thornell,Susann Teneberg

doi:10.1038/s41598-020-76104-3

Abstract

Gastrointestinal stromal tumours (GISTs) are the major nonepithelial neoplasms of the human gastrointestinal tract with a worldwide incidence between 11 and 15 per million cases annually. In this study the acid and non-acid glycosphingolipids of three GISTs were characterized using a combination of thin-layer chromatography, chemical staining, binding of carbohydrate recognizing ligands, and mass spectrometry. In the non-acid glycosphingolipid fractions of the tumors globotetraosylceramide, neolactotetraosylceramide, and glycosphingolipids with terminal blood group A, B, H, Lex, Lea, Ley and Leb determinants were found. The relative amounts of these non-acid compounds were different in the three tumour samples. The acid glycosphingolipid fractions had sulfatide, and the gangliosides GM3, GD3, GM1, Neu5Acα3neolactotetraosylceramide, GD1a, GT1b and GQ1b. In summary, we have characterized the glycosphingolipids of GISTs and found that the pattern differs in tumours from different individuals. This detailed characterization of glycosphingolipid composition of GISTs could contribute to recognition of new molecular targets for GIST treatment and sub-classification.

Highlights

Gastrointestinal stromal tumours (GISTs) are the major nonepithelial neoplasms of the human gastrointestinal tract with a worldwide incidence between 11 and 15 per million cases annually
Around 80% of GISTs have a mutation in the KIT tyrosine kinase gene, and just over 5% have a mutation in the KIT-homologous tyrosine kinase platelet-derived growth factor receptor alpha (PDGFRA) gene[3]
The total acid fractions isolated from GIST I and II are shown in Fig. 1A,B, lanes 4 and 5

Summary

Introduction

Gastrointestinal stromal tumours (GISTs) are the major nonepithelial neoplasms of the human gastrointestinal tract with a worldwide incidence between 11 and 15 per million cases annually. The most common mesenchymal neoplasms of the human gastrointestinal tract are gastrointestinal stromal tumours (GISTs) These tumours are rare, and the incidence is between 11 and 15 cases/million/year worldwide. Altered glycosylation is a common feature of cancer cells, and an increase in fucosylation, sialylation, and branching of glycans, is often found[8,9,10] These changes may affect any type of glycoconjugate, such as N-glycans and O-glycans on glycoproteins, glycosphingolipids or proteoglycans. The present study is the first investigation of glycosphingolipids in GISTs. Acid and non-acid glycosphingolipids were isolated from three gastric tumours, and the glycosphingolipid fractions obtained were characterized by mass spectrometry and by binding of a battery of carbohydrate recognizing ligands. The relative amounts of the non-acid compounds were different in the three tumour samples This characterization of the glycosphingolipid patterns in GISTs might contribute to the development of new prognosis markers and therapeutic approaches

Methods

Results

Conclusion