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Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro

Evidence has pointed to brain tumor stem cells (BTSC) as culprits behind human high-grade glioma (hHGG) resistance to standard therapy. Pre-clinical rodent models are the mainstay for testing of new therapeutic strategies. The typical model involves the intracranial injection of human glioma cells i...

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Autores principales: Binello, Emanuela, Qadeer, Zulekha A., Kothari, Harini P., Emdad, Luni, Germano, Isabelle M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328782/
https://www.ncbi.nlm.nih.gov/pubmed/22514559
http://dx.doi.org/10.7150/jca.4149
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author Binello, Emanuela
Qadeer, Zulekha A.
Kothari, Harini P.
Emdad, Luni
Germano, Isabelle M.
author_facet Binello, Emanuela
Qadeer, Zulekha A.
Kothari, Harini P.
Emdad, Luni
Germano, Isabelle M.
author_sort Binello, Emanuela
collection PubMed
description Evidence has pointed to brain tumor stem cells (BTSC) as culprits behind human high-grade glioma (hHGG) resistance to standard therapy. Pre-clinical rodent models are the mainstay for testing of new therapeutic strategies. The typical model involves the intracranial injection of human glioma cells into immunocompromised hosts, hindering the evaluation of tumor-host responses and resulting in non-infiltrative tumors. The CT-2A model is an immunocompetent mouse model with potential to overcome these disadvantages. In this study, we confirmed the highly infiltrative nature of intracranial CT-2A tumors and optimized reproducible injection parameters. We then generated neurospheres and established, for the first time, the stemness of this model. CT-2A expression of the BTSC marker, CD133, increased from 2% in monolayer cells to 31% in fully-formed neurospheres. Investigation of three stem cell markers (Oct4, Nanog and Nestin) revealed a distinct stemness signature with monolayer cells expressing Oct4 and Nestin (no Nanog), and neurospheres expressing all three. Additionally, CT-2A cells were more proliferative and invasive than U87 cells, while CT-2A neurospheres were significantly more proliferative and invasive than either monolayer cells in vitro. Taken together, our results show that this model is a valuable tool for pre-clinical testing of novel therapeutics against hHGG and also affords the opportunity for investigation of BTSC in an immunocompetent setting.
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spelling pubmed-33287822012-04-18 Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro Binello, Emanuela Qadeer, Zulekha A. Kothari, Harini P. Emdad, Luni Germano, Isabelle M. J Cancer Research Paper Evidence has pointed to brain tumor stem cells (BTSC) as culprits behind human high-grade glioma (hHGG) resistance to standard therapy. Pre-clinical rodent models are the mainstay for testing of new therapeutic strategies. The typical model involves the intracranial injection of human glioma cells into immunocompromised hosts, hindering the evaluation of tumor-host responses and resulting in non-infiltrative tumors. The CT-2A model is an immunocompetent mouse model with potential to overcome these disadvantages. In this study, we confirmed the highly infiltrative nature of intracranial CT-2A tumors and optimized reproducible injection parameters. We then generated neurospheres and established, for the first time, the stemness of this model. CT-2A expression of the BTSC marker, CD133, increased from 2% in monolayer cells to 31% in fully-formed neurospheres. Investigation of three stem cell markers (Oct4, Nanog and Nestin) revealed a distinct stemness signature with monolayer cells expressing Oct4 and Nestin (no Nanog), and neurospheres expressing all three. Additionally, CT-2A cells were more proliferative and invasive than U87 cells, while CT-2A neurospheres were significantly more proliferative and invasive than either monolayer cells in vitro. Taken together, our results show that this model is a valuable tool for pre-clinical testing of novel therapeutics against hHGG and also affords the opportunity for investigation of BTSC in an immunocompetent setting. Ivyspring International Publisher 2012-04-12 /pmc/articles/PMC3328782/ /pubmed/22514559 http://dx.doi.org/10.7150/jca.4149 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
spellingShingle Research Paper
Binello, Emanuela
Qadeer, Zulekha A.
Kothari, Harini P.
Emdad, Luni
Germano, Isabelle M.
Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro
title Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro
title_full Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro
title_fullStr Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro
title_full_unstemmed Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro
title_short Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro
title_sort stemness of the ct-2a immunocompetent mouse brain tumor model: characterization in vitro
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328782/
https://www.ncbi.nlm.nih.gov/pubmed/22514559
http://dx.doi.org/10.7150/jca.4149
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