Attempts to elucidate the roles of carbohydrate-associated structures in biology have led to the distinct field of glycobiology research. The focus of this field has been in understanding the evolution, biosynthesis and interactions of glycans, both individually and as components of larger bio-molecules. However, as most approaches for studying glycans (including mass spectrometry and various binding assays) use ensemble measurements, they lack the precision required to uncover the roles of glycoconjugates, which are often heterogeneous, in biomolecular processes. Single molecule techniques can examine individual events within challenging mixtures and they are beginning to be applied to glycobiology. For example, single molecule force spectroscopy (SMFS) by atomic force microscopy (AFM) has enabled the molecular interactions of sugars to be studied, single molecule fluorescence microscopy and spectroscopy have led to insight into the role of sugars in biological processes and nanopores have revealed key interactions between polysaccharides and their transporters. Thus, single molecule technology is becoming a valuable tool in glycoscience.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains important. The neuropilin-1 (NRP-1) receptor has recently been implicated in tumor progression of MB, which seems to play an important role in the phenotype of cancer stem cells. Targeting this receptor appears as an interesting strategy to promote MB stem cells differentiation. Cancer stem-like cells of 3 MB cell lines (DAOY, D283-Med and D341-Med), classified in the more pejorative molecular subgroups, were obtained by in vitro enrichment. These models were characterized by an increase of NRP-1 and cancer stem cell markers (CD15, CD133 and Sox2), meanwhile a decrease of the differentiated cell marker Neurofilament-M (NF-M) was observed. Our previous work investigated potential innovative peptidomimetics that specifically target NRP-1 and showed that MR438 had a good affinity for NRP-1. This small molecule decreased the self-renewal capacity of MB stem cells for the 3 cell lines and reduced the invasive ability of DAOY and D283 stem cells while NRP-1 expression and cancer stem cell markers decreased at the same time. Possible molecular mechanisms were explored and showed that the activation of PI3K/AKT and MAPK pathways significantly decreased for DAOY cells after treatment. Finally, our results highlighted that targeting NRP-1 with MR438 could be a potential new strategy to differentiate MB stem cells and could limit medulloblastoma progression.
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