Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media
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Noemí García-Romero1,*, Carmen González-Tejedo2,*, Josefa Carrión-Navarro3,*, Susana Esteban-Rubio4, Gorjana Rackov1, Vanessa Rodríguez-Fanjul1, Jorge Oliver-De La Cruz5, Ricardo Prat-Acín6, María Peris-Celda6, David Blesa7, Laura Ramírez-Jiménez7, Pilar Sánchez-Gómez8, Rosario Perona9, Carmen Escobedo-Lucea10, Cristobal Belda-Iniesta3, Angel Ayuso-Sacido1,3,4
1Instituto Madrileño de Estudios Avanzados, IMDEA Nanociencia, Madrid, Spain
2Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain
3Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain
4Instituto de Medicina Molecular Aplicada (IMMA), School of Medicine, San Pablo-CEU University, Campus de Montepríncipe, Madrid, Spain
5International Clinical Research Center, Center for Translational Medicine, St. Anne’s University Hospital, Brno, Czech Republic
6Neurosurgery Department, Hospital Universitario la Fe de Valencia, Valencia, Spain
7Genetic and Genomic Unit, Fundación Centro de Investigación Príncipe Felipe, Valencia, Spain
8Neuro-oncology Unit, Instituto de Salud Carlos III-UFIEC, Madrid, Spain
9Instituto de Investigaciones Biomédicas, CIBERER, CSIC/UAM, Madrid, Spain
10Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki, Helsinki, Finland
*These authors have contributed equally to this work
Angel Ayuso-Sacido, email: email@example.com
Keywords: cancer stem cells, glioblastoma, genetic alterations, drug discovery, primary cell culture
Received: May 30, 2016 Accepted: August 17, 2016 Published: August 29, 2016
Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas.
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