title: A proteomic investigation into etoposide chemo-resistance of neuroblastoma cell lines.
abstract: Neuroblastoma, one of the most common pediatric solid tumors, originates from the peripheral sympathetic nervous system and is responsible for approximately 15% of all childhood cancer deaths. Among the several antineoplastic drugs used in neuroblastoma chemotherapeutic protocols, topoisomerase inhibitors (i.e., etoposide) represent the most commonly used. Several resistance mechanisms limit the clinical success of topoisomerase-targeting drugs, mainly reducing the ability of neoplastic cells to start programmed cell death when exposed to antineoplastic drugs. The aim of this study was to determine, by means of proteomics, potential markers of etoposide resistance in human neuroblastoma cell lines as well as to investigate protein levels and modifications possibly involved in the onset of resistance. The etoposide resistant clone showed overexpression of the following proteins: peroxiredoxin 1, beta-galactoside soluble lectin binding protein, vimentin (three protein spots), heat shock 27 kDa protein (two protein spots) and heterogeneous nuclear ribonucleoprotein K. In addition, we also found down-regulation of dUTP pyrophosphatase. This investigation might represent a first step towards the development of novel prognostic markers of neuroblastoma chemotherapy.
authors.affiliation: Centro Studi sull'Invecchiamento (Ce.S.I.), Fondazione Università G. D'Annunzio, Chieti, Italy. a.urbani@unich.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Julia
authors.initials: J
authors.lastname: Poland
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bellincampi
authors.forename: Antonino
authors.initials: A
authors.lastname: Biroccio
authors.forename: Martina
authors.initials: M
authors.lastname: Schnölzer
authors.forename: Pranav
authors.initials: P
authors.lastname: Sinha
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D013058:Mass Spectrometry; D009447:Neuroblastoma / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020543:Proteome; D059005:Topoisomerase II Inhibitors; D005047:Etoposide