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Characterization of a new glioblastoma cell line, GB-val4, with unusual TP53 mutation

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Abstract

A novel cell line derived from a human glioblastoma (GB), named GB-val4, has been established and characterized. GB-val4 cells were hyperdiploid, with many numerical and structural chromosomal rearrangements. The cell line did not show mutations in IDH1/IDH2 genes or EGFR amplification, but it presented two missense mutations in TP53, which imply a very low p53 protein activity within the cell line. Cells also had gain of TP73 copies, hypermethylation of APC, CASP8 and RASSF1, increased expression of ARF1, CDH1 and NF-κB and decreased expression of CDKN2A. Tumorigenity was demonstrated by transplant of GB-val4 cells into athymic nude mice, where solid tumors were grown. Interestingly, a high percentage of GB-val4 cells presented expression of GSC markers CD133 or CD44. These GSC markers were increased in neurosphere cultures, which better mimic solid tumor conditions and maintain the genetic features of the tumor cells. In this study, we aimed to define the characteristics of this novel cell line and its applications in human cancer research. With its genetic features and a poor p53 activity, GB-val4 cells resemble GB tumors. Moreover, the important presence of GSCs in adherent cultures and especially in neurosphere cultures makes GB-val4 an attractive tool to study cancer stem cells, deepen in the knowledge the molecular pathways of GB and develop new therapeutic strategies for patients with these tumors.

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Acknowledgements

Supported by grants PROMETEO 2011-11/83 from the Generalitat Valenciana and PI14/01669 from the Ministerio de Economía y Competividad-Spain (Instituto de Salud Carlos III). We acknowledge to Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA).

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Author notes

  1. Lisandra Muñoz-Hidalgo and Teresa San-Miguel contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine and Odontology, University of Valencia, Avenida de Blasco Ibáñez 15, 46010, Valencia, Spain

    Lisandra Muñoz-Hidalgo, Teresa San-Miguel, Javier Megías, Rosario Gil-Benso, Miguel Cerdá-Nicolás & Concha López-Ginés

  2. Service of Pathology, Clinic Hospital of Valencia, Avenida de Blasco Ibáñez 17, 46010, Valencia, Spain

    Miguel Cerdá-Nicolás

Authors
  1. Lisandra Muñoz-Hidalgo
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  2. Teresa San-Miguel
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  3. Javier Megías
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  4. Rosario Gil-Benso
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  5. Miguel Cerdá-Nicolás
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  6. Concha López-Ginés
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Correspondence to Javier Megías.

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All authors have approved the final version of the article. The authors declare that they have no conflict of interest.

Research involving animals

All assays involving mice were approved by the Institutional Animal Care and Use Committee (University of Valencia) and were carried out in strict accordance with the “Real Decreto 1201/2005, BOE 252” for the Care and Use of Laboratory Animals of the “Ministerio de la Presidencia,” Spain. All efforts were made to minimize suffering.

Informed consent

Approval for the study herein reported was provided by Institutional Ethics Committee of the University of Valencia and Clinic Hospital of Valencia (Ley 14/2007 de Investigación Biomédica, ethics committee approval on 2015/06/03).

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Muñoz-Hidalgo, L., San-Miguel, T., Megías, J. et al. Characterization of a new glioblastoma cell line, GB-val4, with unusual TP53 mutation. Human Cell 32, 557–567 (2019). https://doi.org/10.1007/s13577-019-00267-z

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