Jacob, L. Sawma, P. Garnier, N. Meyer, L. A. Fritz, J. Hussenet, T. Spenle, C. Goetz, J. Vermot, J. Fernandez, A. Baumlin, N. Aci-Seche, S. Orend, G. Roussel, G. Cremel, G. Genest, M. Hubert, P. Bagnard, D.
Oncotarget (2016) 7 (36) 57851-57865 - doi : 10.18632/oncotarget.11072
publié le , mis à jour le
The neuropilin-plexin receptor complex regulates tumor cell migration and proliferation and thus is an interesting therapeutic target. High expression of neuropilin-1 is indeed associated with a bad prognosis in glioma patients. Q-RTPCR and tissue-array analyses showed here that Plexin-A1 is highly expressed in glioblastoma and that the highest level of expression correlates with the worse survival of patients. We next identified a developmental and tumor-associated pro-angiogenic role of Plexin-A1. Hence, by using molecular simulations and a two-hybrid like assay in parallel with biochemical and cellular assays we developed a specific Plexin-A1 peptidic antagonist disrupting transmembrane domain-mediated oligomerization of the receptor and subsequent signaling and functional activity. We found that this peptide exhibits anti-tumor activity in vivo on different human glioblastoma models including glioma cancer stem cells. Thus, screening Plexin-A1 expression and targeting Plexin-A1 in glioblastoma patients exhibit diagnostic and therapeutic value.