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
Citation
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. (2016) Inhibition of PlexA1-mediated brain tumor growth and tumor-associated angiogenesis using a transmembrane domain targeting peptide. Oncotarget. 7:57851-57865.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping