PUBLICATION

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

Authors
Jacob, L., Sawma, P., Garnier, N., Meyer, L.A., Fritz, J., Hussenet, T., Spenlé, C., Goetz, J., Vermot, J., Fernandez, A., Baumlin, N., Aci-Sèche, S., Orend, G., Roussel, G., Crémel, G., Genest, M., Hubert, P., Bagnard, D.
ID
ZDB-PUB-180223-68
Date
2016
Source
Oncotarget   7: 57851-57865 (Journal)
Registered Authors
Vermot, Julien
Keywords
angiogenesis, anti-cancer drug, biomarker, glioblastoma, plexin
MeSH Terms
  • Animals
  • Antineoplastic Agents/pharmacology*
  • Biomarkers, Tumor/metabolism
  • Brain Neoplasms/metabolism
  • Brain Neoplasms/pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chick Embryo
  • Chorioallantoic Membrane/metabolism
  • Glioblastoma/metabolism
  • Glioblastoma/pathology
  • Glioma/metabolism
  • Glioma/pathology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Neovascularization, Pathologic/prevention & control*
  • Nerve Tissue Proteins/antagonists & inhibitors*
  • Nerve Tissue Proteins/metabolism
  • Peptides/pharmacology*
  • Protein Domains
  • Receptors, Cell Surface/antagonists & inhibitors*
  • Receptors, Cell Surface/metabolism
  • Tissue Array Analysis
  • Zebrafish
PubMed
27506939 Full text @ Oncotarget
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping