Abstract:

Tumor hypoxia is a common pathological feature in many cancers. Hypoxic microenvironments dramatically shift the pattern of intracellular glucose metabolism, which increase glucose uptake and nucleotide sugar levels. In this study, hypoxia-induced malignant breast tumor (MDA-MB-231) cell model was established. Under hypoxia conditions, MDA-MB-231 cells showed the fibrosis morphology. Expression level of β-catenin in hypoxia-treated cells was reduced, fibronectin was increased, and cell motility was enhanced, which indicated that hypoxia induces the epithelial-mesenchymal transition. The structures of N-glycans from normoxia and hypoxia-treated cells were further analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Seventeen N-glycans were differentially expressed in normoxia and hypoxia-treated MDA-MB-231 cells. The high-mannose and tetra-antennary type of N-glycans were increased, while the hybrid type, bisecting type, biantennary type, triantennary type, fucosylation and sialylation of N-glycans were decreased in hypoxia-treated MDA-MB-231 cells. The study of lectin Con A and LCA fluorescence staining consistented with MS analysis. The present research indicates that hypoxia alters the expression of N-glycans in malignant breast tumor cells, which may provide the fundamental observations for further understanding functional roles of differential expression of N-glycans in hypoxia-treated cells．

Key words:  , hypoxia； epithelial-mesenchymal transition； MALDI-TOF/TOF-MS； N-glycan