title: 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.
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Laurent
authors: L
authors: Jacob
authors: Laboratoire d’Ingénierie des Systèmes Macromoléculaires (LISM), UMR 7255, CNRS-Aix Marseille Université, Marseille, France.
authors: Paul
authors: P
authors: Sawma
authors: Centre de Biophysique Moléculaire, UPR 4301, CNRS, Affiliated to the University of Orléans, Orléans, France.
authors: Norbert
authors: N
authors: Garnier
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Lionel A T
authors: LA
authors: Meyer
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Justine
authors: J
authors: Fritz
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Thomas
authors: T
authors: Hussenet
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Caroline
authors: C
authors: Spenlé
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.|Institute of Genetics and Molecular and Cellular Biology (IGBMC), CNRS/INSERM/UDS, Illkirch, France.
authors: Jacky
authors: J
authors: Goetz
authors: Institute of Genetics and Molecular and Cellular Biology (IGBMC), CNRS/INSERM/UDS, Illkirch, France.
authors: Julien
authors: J
authors: Vermot
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Aurore
authors: A
authors: Fernandez
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Nadège
authors: N
authors: Baumlin
authors: Centre de Biophysique Moléculaire, UPR 4301, CNRS, Affiliated to the University of Orléans, Orléans, France.|Current address: Institut de Chimie Organique et Analytique UMR, Université d'Orléans, Orléans, France.
authors: Samia
authors: S
authors: Aci-Sèche
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Gertraud
authors: G
authors: Orend
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Guy
authors: G
authors: Roussel
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Gérard
authors: G
authors: Crémel
authors: Centre de Biophysique Moléculaire, UPR 4301, CNRS, Affiliated to the University of Orléans, Orléans, France.
authors: Monique
authors: M
authors: Genest
authors: Laboratoire d’Ingénierie des Systèmes Macromoléculaires (LISM), UMR 7255, CNRS-Aix Marseille Université, Marseille, France.
authors: Pierre
authors: P
authors: Hubert
authors: MN3T Team, INSERM U1109, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|LabEx Medalis, Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: Dominique
authors: D
authors: Bagnard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D000072417:Protein Domains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D046888:Tissue Array Analysis; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; C492116:PLXNA1 protein, human; D010455:Peptides; D011956:Receptors, Cell Surface
keywords: angiogenesis; anti-cancer drug; biomarker; glioblastoma; plexin