The Functional Role of N-glycans on Galectin-3 Binding Protein in Breast Cancer Cell Metastasis

• Main Authors: Hui-Tzu Chang, 張慧慈
• Other Authors: Chi-Huey Wong
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/uhq6hq

博士 === 國立陽明大學 === 生化暨分子生物研究所 === 105 === Galectin-3 binding protein (Gal-3BP) is a large hyperglycosylated protein that binds to galectins through its glycans. Gal-3BP can induce galectin-mediated tumor cell aggregation to maintain the survival of cancer cells in the bloodstream during the metastatic process. However, due to the limitation of mass spectrometry in glycan sequencing, the glycans on Gal-3BP that mediate the binding to galectins are yet to be elucidated. To understand the role of Gal-3BP, we here used liquid chromatography− mass spectrometry combined with specific exoglycosidase reactions to determine the sequences of N-glycans on Gal-3BP. We compared N-glycans on Gal-3BPs from two breast cancer cell lines, MCF-7 and MDA-MB-231 cells, with different degrees of aggressiveness, especially the sequences with terminal sialylation and fucosylation, and addition of LacNAc repeat structures. The N-glycans from both cell lines are complex type with terminal α2,3 sialic acid and core fucose linkages, and with additional α1,2- and α1,3 fucose linkages found in MCF-7 cells. Compared with that in MCF-7, the Gal-3BP from MDA-MB-231 cells had fewer tetra-antennary structures, with only α1,6-linked core fucoses, and with more LacNAc repeat structures; the MDA-MB-231 cells had no surface galectin-3 but used surface galectin-1 for interaction with Gal-3BP to form large cell aggregates. Through analysis of the sequences of N-glycans on Gal-3BP from different aggressive breast cancer cell lines, this study elucidates the specificity of Gal-3BP interacting with galectin-1 and the role of Gal-3BP in cancer cell aggregation and metastasis.