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

被引：31

作者：

Jacob, Laurent ^{[1
,2
,3
,4
]}

Sawma, Paul ^{[5
]}

Garnier, Norbert ^{[6
]}

Meyer, Lionel A. T. ^{[1
,2
,3
,4
]}

Fritz, Justine ^{[1
,2
,3
,4
]}

Hussenet, Thomas ^{[1
,2
,3
,4
]}

Spenle, Caroline ^{[1
,2
,3
,4
]}

Goetz, Jacky ^{[1
,2
,3
,4
,7
]}

Vermot, Julien ^{[7
]}

Fernandez, Aurore ^{[1
,2
,3
,4
]}

Baumlin, Nadege ^{[1
,2
,3
,4
]}

Aci-Seche, Samia ^{[6
,8
]}

Orend, Gertraud ^{[1
,2
,3
,4
]}

Roussel, Guy ^{[1
,2
,3
,4
]}

Cremel, Gerard ^{[1
,2
,3
,4
]}

Genest, Monique ^{[6
]}

Hubert, Pierre ^{[5
]}

Bagnard, Dominique ^{[1
,2
,3
,4
]}

机构：

[1] INSERM, U1109, Team MN3T, Strasbourg, France

[2] Univ Strasbourg, Strasbourg, France

[3] Univ Strasbourg, LabEx Medalis, Strasbourg, France

[4] FMTS, Strasbourg, France

[5] Aix Marseille Univ, CNRS, LISM, UMR 7255, Marseille, France

[6] Univ Orleans, CNRS, Ctr Biophys Mol, UPR 4301, F-45067 Orleans, France

[7] CNRS INSERM UDS, Inst Genet & Mol & Cellular Biol IGBMC, Illkirch Graffenstaden, France

[8] Univ Orleans, Inst Chim Organ & Analyt UMR, Orleans, France

来源：

ONCOTARGET | 2016年 / 7卷 / 36期

关键词：

plexin; anti-cancer drug; angiogenesis; biomarker; glioblastoma; ANTIANGIOGENIC THERAPIES; MOLECULAR SIMULATION; EGF RECEPTOR; STEM-CELLS; NEUROPILIN-1; CANCER; GLIOBLASTOMA; GLIOMA; ACTIVATION; MEMBRANE;

D O I：

10.18632/oncotarget.11072

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：57851 / 57865

页数：15

共 42 条

[1] Transmembrane Recognition of the Semaphorin Co-Receptors Neuropilin 1 and Plexin A1: Coarse-Grained Simulations [J].