Oncotarget

Research Papers:

Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic targeting neuropilin-1

Caifeng Gong _, Julie Valduga, Alicia Chateau, Mylène Richard, Nadia Pellgrini-Moïse, Muriel Barberi-Heyob, Pascal Chastagner and Cédric Boura

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:15312-15325. https://doi.org/10.18632/oncotarget.24521

Metrics: PDF 1142 views  |   HTML 2506 views  |   ?  


Abstract

Caifeng Gong1, Julie Valduga1,2, Alicia Chateau1, Mylène Richard3, Nadia Pellegrini-Moïse3, Muriel Barberi-Heyob1, Pascal Chastagner1,2 and Cédric Boura1

1Université de Lorraine, CNRS, CRAN, F-54000 Nancy, France

2Service d'Onco-Hématologie Pédiatrique, CHRU-Nancy, F-54000 Nancy, France

3Université de Lorraine, CNRS, L2CM, F-54000 Nancy, France

Correspondence to:

Cédric Boura, email: cedric.boura@univ-lorraine.fr

Keywords: medulloblastoma; neuropilin-1; cancer stem cells; peptidomimetic; cell differentiation

Received: July 07, 2017     Accepted: February 10, 2018     Epub: February 16, 2018     Published: March 16, 2018

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 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 24521