Oncotarget

Priority Research Papers:

Stem cell cultures derived from pediatric brain tumors accurately model the originating tumors

Anna Wenger, Susanna Larsson, Anna Danielsson, Kirstine Juul Elbæk, Petronella Kettunen, Magnus Tisell, Magnus Sabel, Birgitta Lannering, Claes Nordborg, Elizabeth Schepke, Helena Carén _

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Abstract

Anna Wenger1, Susanna Larsson1, Anna Danielsson2, Kirstine Juul Elbæk1, Petronella Kettunen3,4, Magnus Tisell5, Magnus Sabel6,7, Birgitta Lannering6,7, Claes Nordborg8, Elizabeth Schepke1,7 and Helena Carén1

1 Department of Pathology, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden

2 Department of Oncology, Sahlgrenska Cancer Center, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden

3 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden

4 Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

5 Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden

6 Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden

7 The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden

8 Department of Pathology, Sahlgrenska University Hospital, Sweden

Correspondence to:

Helena Carén, email:

Keywords: DNA methylation, pediatric, glioblastoma, cancer stem cells, immunodeficient mice

Received: October 29, 2016 Accepted: January 16, 2017 Published: January 26, 2017

Abstract

Brain tumors are the leading cause of cancer-related death in children but high-grade gliomas in children and adolescents have remained a relatively under-investigated disease despite this. A better understanding of the cellular and molecular pathogenesis of the diseases is required in order to improve the outcome for these children. In vitro-cultured primary tumor cells from patients are indispensable tools for this purpose by enabling functional analyses and development of new therapies. However, relevant well-characterized in vitro cultures from pediatric gliomas cultured under serum-free conditions have been lacking. We have therefore established patient-derived in vitro cultures and performed thorough characterization of the cells using large-scale analyses of DNA methylation, copy-number alterations and investigated their stability during prolonged time in culture. We show that the cells were stable during prolonged culture in serum-free stem cell media without apparent alterations in morphology or growth rate. The cells were proliferative, positive for stem cell markers, able to respond to differentiation cues and initiated tumors in zebrafish and mice suggesting that the cells are cancer stem cells or progenitor cells. The cells accurately mirrored the tumor they were derived from in terms of methylation pattern, copy number alterations and DNA mutations. These unique primary in vitro cultures can thus be used as a relevant and robust model system for functional studies on pediatric brain tumors.

Author Information

Anna Wenger

Susanna Larsson

Anna Danielsson

Kirstine Juul Elbæk

Petronella Kettunen

Magnus Tisell

Magnus Sabel

Birgitta Lannering

Claes Nordborg

Elizabeth Schepke

Helena Carén
Primary Contact  _


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