Human Medulloblastoma Cell Lines: Investigating on Cancer Stem Cell-Like Phenotype

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differentiation potential is critical for tumor initiation, growth, and resistance to therapies. For the development of new CSC-targeted therapies, further in-depth studies are needed using enriched and stable MB-CSCs populations. This work, aimed at identifying the amount of CSCs in three available human cell lines (DAOY, D341, and D283), describes different approaches based on the expression of stemness markers. First, we explored potential differences in gene and protein expression patterns of specific stem cell markers. Then, in order to identify and discriminate undifferentiated from differentiated cells, MB cells were characterized using a physical characterization method based on a high-frequency dielectrophoresis approach. Finally, we compared their tumorigenic potential in vivo, through engrafting in nude mice. Concordantly, our findings identified the D283 human cell line as an ideal model of CSCs, providing important evidence on the use of a commercial human MB cell line for the development of new strategic CSC-targeting therapies.

The Expression of the Cancer-Associated lncRNA Snhg15 Is Modulated by EphrinA5-Induced Signaling

“…Among the lncRNAs, we identified Snhg15 as significantly reduced in expression in response to ephrinA5 stimulation in CB cells. An ephrinA5-Fc triggered reduction in SNHG15 was further observed in DAOY cells, a human medulloblastoma cell line [ 26 ]. Snhg15 is known to be involved in proliferation and migration regulation in various human cancer types [ 13 ].…”

Microsecond Pulsed Electric Fields: An Effective Way to Selectively Target and Radiosensitize Medulloblastoma Cancer Stem Cells

“…As previously demonstrated, subcutaneous implantation of 6 Â 10 6 D283 cells in nude mice was sufficient to ensure 100% of tumor engraftment within 12 days postinjection. 20 To verify PEF-5's efficacy in modifying the tumorigenic potential of D283 cells, treated and sham-treated cells were implanted in the right flank of CD1 nude mice. PEF-5 exposure significantly delayed tumor growth compared with the sham group, with a final tumor growth inhibition (TGI%) of 46.47% at 43 days post-treatment, indicating that PEF-5 alone is sufficient to affect the tumor growth significantly (Fig.…”

“…18 Medulloblastoma (MB), a highly malignant primitive neuroectodermal tumor of the cerebellum, represents about 20% of all childhood primary tumors of the central nervous system. 19 To test the potential efficacy of msPEF on MB CSCs, we analyzed different in vitro endpoints on D283Med cells, reportedly rich in CSCs, 20 and on a normal human astrocyte (NHA) primary cell line. We evaluated cell permeabilization and reactive oxygen species (ROS) production, cell viability, growth rate, cell cycle, and perturbation of molecular pathways.…”

Microfluidic Lab-On-a-Chip based on UHF-Dielectrophoresis for Stemness Phenotype Characterization and Discrimination among Glioblastoma Cells

“…Hence, cells can be individually electro-manipulated by the DEP force motion according to their own dielectric properties of their cytoplasm. As an example, UHF-DEP has already been successfully used in order to discriminate differentiated from undifferentiated medulloblastoma cells [19,20]. This paper aims to show the relevance of the identification of the crossover frequency fx02 as the DEP signature and then, using it as an appropriate discriminant biomarker to detect CSCs within tumor cell population.…”