title: Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.
abstract: 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.
authors: Instituto Madrileño de Estudios Avanzados, IMDEA Nanociencia, Madrid, Spain.
authors: Noemí
authors: N
authors: García-Romero
authors: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors: Carmen
authors: C
authors: González-Tejedo
authors: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.
authors: Josefa
authors: J
authors: Carrión-Navarro
authors: Instituto de Medicina Molecular Aplicada (IMMA), School of Medicine, San Pablo-CEU University, Campus de Montepríncipe, Madrid, Spain.
authors: Susana
authors: S
authors: Esteban-Rubio
authors: Instituto Madrileño de Estudios Avanzados, IMDEA Nanociencia, Madrid, Spain.
authors: Gorjana
authors: G
authors: Rackov
authors: Instituto Madrileño de Estudios Avanzados, IMDEA Nanociencia, Madrid, Spain.
authors: Vanessa
authors: V
authors: Rodríguez-Fanjul
authors: International Clinical Research Center, Center for Translational Medicine, St. Anne's University Hospital, Brno, Czech Republic.
authors: Jorge
authors: J
authors: Oliver-De La Cruz
authors: Neurosurgery Department, Hospital Universitario la Fe de Valencia, Valencia, Spain.
authors: Ricardo
authors: R
authors: Prat-Acín
authors: Neurosurgery Department, Hospital Universitario la Fe de Valencia, Valencia, Spain.
authors: María
authors: M
authors: Peris-Celda
authors: Genetic and Genomic Unit, Fundación Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors: David
authors: D
authors: Blesa
authors: Genetic and Genomic Unit, Fundación Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors: Laura
authors: L
authors: Ramírez-Jiménez
authors: Neuro-Oncology Unit, Instituto de Salud Carlos III-UFIEC, Madrid, Spain.
authors: Pilar
authors: P
authors: Sánchez-Gómez
authors: Instituto de Investigaciones Biomédicas, CIBERER, CSIC/UAM, Madrid, Spain.
authors: Rosario
authors: R
authors: Perona
authors: Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki, Helsinki, Finland.
authors: Carmen
authors: C
authors: Escobedo-Lucea
authors: Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.
authors: Cristobal
authors: C
authors: Belda-Iniesta
authors: Instituto Madrileño de Estudios Avanzados, IMDEA Nanociencia, Madrid, Spain.|Fundación de Investigación HM Hospitales, HM Hospitales, Madrid, Spain.|Instituto de Medicina Molecular Aplicada (IMMA), School of Medicine, San Pablo-CEU University, Campus de Montepríncipe, Madrid, Spain.
authors: Angel
authors: A
authors: Ayuso-Sacido
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016895:Culture Media, Serum-Free
keywords: cancer stem cells; drug discovery; genetic alterations; glioblastoma; primary cell culture