title: Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells-Characterization of a New in Vivo Model.
abstract: Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells' invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats' behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Siniša Stankovi&#263;", University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia. sonja.stojkovic@ibiss.bg.ac.rs.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stojković
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Siniša Stankovi&#263;", University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia. ana.podolski@ibiss.bg.ac.rs.
authors.forename: Ana
authors.initials: A
authors.lastname: Podolski-Renić
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Siniša Stankovi&#263;", University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia. jelena.dinic@ibiss.bg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Dinić
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Siniša Stankovi&#263;", University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia. zeljko.pavkovic@ibiss.bg.ac.rs.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Pavković
authors.affiliation: Group of Structural Mechanics and Materials Modeling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Aragon 50018, Spain. josayuso@unizar.es.|Arag&#243;n Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain. josayuso@unizar.es.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Madrid, Madrid 28029, Spain. josayuso@unizar.es.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ayuso
authors.affiliation: Group of Structural Mechanics and Materials Modeling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Aragon 50018, Spain. luisf@unizar.es.|Arag&#243;n Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain. luisf@unizar.es.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Madrid, Madrid 28029, Spain. luisf@unizar.es.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Fernández
authors.affiliation: Group of Structural Mechanics and Materials Modeling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Aragon 50018, Spain. iochgar@unizar.es.|Arag&#243;n Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain. iochgar@unizar.es.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Madrid, Madrid 28029, Spain. iochgar@unizar.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ochoa
authors.affiliation: Departamento de Matem&#225;ticas, E.T.S.I. Industriales and Instituto de Matem&#225;tica Aplicada a la Ciencia y la Ingenier&#237;a (IMACI), Universidad de Castilla-La Mancha, Ciudad Real 13071, Spain. Victor.PerezGarcia@uclm.es.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Pérez-García
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Siniša Stankovi&#263;", University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia. vesnav@ibiss.bg.ac.rs.
authors.forename: Vesna
authors.initials: V
authors.lastname: Pešić
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Siniša Stankovi&#263;", University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia. camala@ibiss.bg.ac.rs.
authors.forename: Milica
authors.initials: M
authors.lastname: Pešić
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D009361:Neoplasm Invasiveness; D051381:Rats
chemical_list: D018906:Antineoplastic Agents, Alkylating
keywords: DNA damaging agents; antiglioma therapy; behavior study; chemoresistance; glioma; in vivo model; invasion