Inhibition of PlexA1-mediated brain tumor growth and tumor-associated angiogenesis using a transmembrane domain targeting peptide

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-01407022
Contributor : Isabelle Frapart <>
Submitted on : Thursday, December 1, 2016 - 5:25:58 PM
Last modification on : Wednesday, May 22, 2019 - 10:42:03 AM

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Laurent Jacob, Paul Sawma, Norbert Garnier, Lionel A.T. Meyer, Justine Fritz, et al.. Inhibition of PlexA1-mediated brain tumor growth and tumor-associated angiogenesis using a transmembrane domain targeting peptide. Oncotarget, Impact journals, 2016, ⟨10.18632/oncotarget.11072⟩. ⟨hal-01407022⟩

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