title: Silencing of epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) via siRNA-induced cell death in glioblastoma.
abstract: The failure of therapies targeting tumor angiogenesis may be caused by anti-angiogenic resistance mechanisms induced by VEGF and non-VEGF pathways alterations. Anti-angiogenic therapy failure is also attributed to immune system, acting by tumor-associated macrophages that release pro-angiogenic factors and a consequent increase of blood vessels. Recently, in a study by Rheal et al., a new angiogenic receptor, epidermal growth factor, latrophilin, and 7 trans-membrane domain-containing protein 1 on chromosome 1(ELTD1) has been identified as a promising glioma biomarker. In this study we aim to analyse whether this receptor may be used as a target molecule in glioblastoma therapy. Our results showed that small interfering RNA silencing ELTD1 caused cytotoxicity in glioblastoma cells. We also found that PDGFR, VEGFR, and their common PI3K/mTOR intracellular pathway inactivation-induced cytotoxicity in glioblastoma cells. Further, we found high percent of cytotoxicity in a low passage glioblastoma cell line after BEZ235 (a dual inhibitor of PI3K/mTOR pathway) treatment at nanomolar concentrations, compared to AG1433 (a PDGFR inhibitor) and SU1498 (a VEGFR inhibitor) that were only cytotoxic at micromolar ranges. In the future, these could prove as attractive therapeutic targets in single therapy or coupled with classic therapeutic approaches such as chemotherapy of radiotherapy.
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Florentina
authors.initials: F
authors.lastname: Serban
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Daianu
authors.affiliation: b Department of Neurosurgery , "Bagdasar-Arseni" Emergency Hospital , Bucharest , Romania.
authors.forename: Ligia Gabriela
authors.initials: LG
authors.lastname: Tataranu
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Stefan-Alexandru
authors.initials: SA
authors.lastname: Artene
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Emami
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Georgescu
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Alexandru
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Stefana Oana
authors.initials: SO
authors.lastname: Purcaru
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Daniela Elise
authors.initials: DE
authors.lastname: Tache
authors.affiliation: c Department of Oncology , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Maria Mihaela
authors.initials: MM
authors.lastname: Danciulescu
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Veronica
authors.initials: V
authors.lastname: Sfredel
authors.affiliation: a Department of Functional Sciences , University of Medicine and Pharmacy of Craiova , Craiova , Romania.
authors.forename: Anica
authors.initials: A
authors.lastname: Dricu
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D020868:Gene Silencing / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics
chemical_list: C428324:ADGRL4 protein, human; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C034800:alpha-latrotoxin receptor; D004815:Epidermal Growth Factor
keywords: ELTD1; PDGFR; PI3K/mTOR pathway; VEGFR; glioblastoma