Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media

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 culture...

Descripción completa

Detalles Bibliográficos
Autores: García-Romero, Noemí, González-Tejedo, Carmen, Carrión-Navarro, Josefa, Esteban-Rubio, Susana, Rackov, Gorjana, Rodríguez-Fanjul, Vanessa, Oliver-De La Cruz, Jorge, Prat-Acín, Ricardo, Peris-Celda, María, Blesa, David, Ramírez-Jiménez, Laura, Sánchez-Gómez, Pilar, Perona, Rosario, Escobedo-Lucea, Carmen, Belda-Iniesta, Cristobal, Ayuso-Sacido, Angel
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7892
Acceso en línea:http://hdl.handle.net/20.500.12105/7892
Access Level:acceso abierto
Palabra clave:Animals
Antineoplastic Agents
Apoptosis
Biomarkers, Tumor
Brain Neoplasms
Cell Culture Techniques
Cell Proliferation
Culture Media, Serum-Free
Female
Glioblastoma
Humans
In Vitro Techniques
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplastic Stem Cells
Prognosis
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Descripción
Sumario: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.