Browsing by Author "Cousin, Jonathan Martin"

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Glycodendrimers : tools to study multivalent galectin-1 interactions
(Montana State University - Bozeman, College of Letters & Science, 2015) Cousin, Jonathan Martin; Chairperson, Graduate Committee: Mary J. Cloninger
Galectin-1 is a carbohydrate binding protein that mediates cancer processes through multivalent interactions with glycoproteins expressed on the surface of cancer cells and in the extracellular matrix. A series of multivalent PAMAM dendrimers were functionalized with lactose and applied to the study and mediation of multivalent galectin-1 interactions. An ELISA was designed to study the interaction of galectin-1 with surface immobilized glycodendrimers. The results of the ELISAs indicate that galectin-1 binds well to the multivalent framework. DLS and fluorescence microscopy were used to study that interaction of galectin-1 with glycodendrimers in solution. These solution-based assays indicate that the glycodendrimers nucleate galectin-1 into nanoparticles. The ability of the glycodendrimers to organize the galectin-1 into biologically active arrays was investigated in cellular assays. A homotypic cellular aggregation assay using DU145 human prostate carcinoma cells, which express a putative galectin-1 ligand (Mucin1), was designed to study the influence of multivalent glycodendrimers on cellular aggregation/tumor formation. All generations of glycodendrimers were observed to inhibit cellular aggregation by diverting the galectin-1 from its native role in cellular cross-linking of cancer cells. To further probe multivalent interactions in cancer, the glycodendrimers were applied to a tube formation assay to study galectin-1 angiogenic processes. Galectin-1 was observed to accelerate neovascularization, and the impact of the galectin-1 was mildly inhibited by the glycodendrimers.