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Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

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 i...

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Autores principales: Stojković, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Pavković, Željko, Ayuso, Jose M., Fernández, Luis J., Ochoa, Ignacio, Pérez-García, Victor M., Pešić, Vesna, Pešić, Milica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273839/
https://www.ncbi.nlm.nih.gov/pubmed/27355941
http://dx.doi.org/10.3390/molecules21070843
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author Stojković, Sonja
Podolski-Renić, Ana
Dinić, Jelena
Pavković, Željko
Ayuso, Jose M.
Fernández, Luis J.
Ochoa, Ignacio
Pérez-García, Victor M.
Pešić, Vesna
Pešić, Milica
author_facet Stojković, Sonja
Podolski-Renić, Ana
Dinić, Jelena
Pavković, Željko
Ayuso, Jose M.
Fernández, Luis J.
Ochoa, Ignacio
Pérez-García, Victor M.
Pešić, Vesna
Pešić, Milica
author_sort Stojković, Sonja
collection PubMed
description 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.
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spelling pubmed-62738392018-12-28 Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model Stojković, Sonja Podolski-Renić, Ana Dinić, Jelena Pavković, Željko Ayuso, Jose M. Fernández, Luis J. Ochoa, Ignacio Pérez-García, Victor M. Pešić, Vesna Pešić, Milica Molecules Article 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. MDPI 2016-06-27 /pmc/articles/PMC6273839/ /pubmed/27355941 http://dx.doi.org/10.3390/molecules21070843 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stojković, Sonja
Podolski-Renić, Ana
Dinić, Jelena
Pavković, Željko
Ayuso, Jose M.
Fernández, Luis J.
Ochoa, Ignacio
Pérez-García, Victor M.
Pešić, Vesna
Pešić, Milica
Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
title Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
title_full Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
title_fullStr Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
title_full_unstemmed Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
title_short Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
title_sort resistance to dna damaging agents produced invasive phenotype of rat glioma cells—characterization of a new in vivo model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273839/
https://www.ncbi.nlm.nih.gov/pubmed/27355941
http://dx.doi.org/10.3390/molecules21070843
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