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.

The IDH-Tau-EGFR triad defines diffuse glioma pathology by controlling mesenchymal differentiation and neo-vascular fitness

“…6L and M), which suggest that Tau represses the growth of EGFRamp/wt glioma growth by blocking the plasticity of tumor cells and the appearance of mesenchymal features. Previous results from our group and others have shown that, in comparison with PN cancer stem cells (CSCs), MES CSCs are more capable of glioma initiation, probably associated with their increased angiogenic capacity (22,23). In agreement with this observation, the overexpression of Tau in RG1 cells impaired their capacity to form subcutaneous xenografts ( fig.…”

Patient‑derived orthotopic xenograft glioma models fail to replicate the magnetic resonance imaging features of the original patient tumor

“…H&E staining of the nodular xenograft portion and of the original patient tumor indicated that the boundary of the xenograft was clear, whereas in the original patient tumor, the boundaries were unclear. Although there was only one case with nodular growth, it was reported that gliomas had nodular growth in mice models and had relatively clear boundaries with normal brain tissue (31)(32)(33). These results show there were notable differences in the MRI characteristics between patient-derived orthotopic xenograft models and the corresponding original tumors.…”

TLR4 interaction with LPS in glioma CD133+ cancer stem cells induces cell proliferation, resistance to chemotherapy and evasion from cytotoxic T lymphocyte-induced cytolysis

“…CSCs possess biological characteristics such as rapid repair of damaged DNA [ 12 , 13 ], metabolic reprogramming [ 14 ], adaption to hyperinflammatory microenvironments [ 10 ], and resistance to oxidative stress and anticancer drugs [ 10 , 15 ]. Evidence indicates that malignant glioma CSCs induce cancer and promote cancer development [ 16 , 17 ]. Moreover, glioma CSCs promote cancer resistance to treatment and recurrence, leading to high mortality [ 18 ].…”