Abstract
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 to be an interesting strategy to promote MB stem cells differentiation. Cancer stem-like cells of 3 MB cell lines (DAOY, D283-Med and Med-D341) in different 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 diminution of the differentiated cell marker Neurofilament-M (NF-M) was observed. Our previous work investigated several potential innovative peptidomimetics that specifically targeted 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 phosphorylation of AKT and ERK proteins in PI3K/AKT and MAPK pathways significantly decreased for DAOY-MS cells after treatment. Finally, our results highlighted that targeting NRP-1 with MR438 is a potential new strategy to differentiate MB stem cells and improve chance to cure.