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.
- Klíčová slova
- cancer stem cells, drug discovery, genetic alterations, glioblastoma, primary cell culture,
- MeSH
- apoptóza MeSH
- buněčné kultury metody MeSH
- glioblastom farmakoterapie metabolismus patologie MeSH
- kultivační média bez séra farmakologie MeSH
- lidé MeSH
- myši inbrední BALB C MeSH
- myši nahé MeSH
- myši MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buňky kultivované MeSH
- nádorové kmenové buňky účinky léků metabolismus patologie MeSH
- nádory mozku farmakoterapie metabolismus patologie MeSH
- prognóza MeSH
- proliferace buněk MeSH
- protinádorové látky farmakologie MeSH
- techniky in vitro MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kultivační média bez séra MeSH
- nádorové biomarkery MeSH
- protinádorové látky MeSH