Tumor-initiating cells with stem cell properties are believed to sustain the growth of gliomas, but proposed markers such as CD133 cannot be used to identify these cells with sufficient specificity. We report an alternative isolation method purely based on phenotypic qualities of glioma-initiating cells (GICs), avoiding the use of molecular markers. We exploited intrinsic autofluorescence properties and a distinctive morphology to isolate a subpopulation of cells (FL1(+)) from human glioma or glioma cultures. FL1(+) cells are capable of self-renewal in vitro, tumorigenesis in vivo and preferentially express stem cell genes. The FL1(+) phenotype did not correlate with the expression of proposed GIC markers. Our data propose an alternative approach to investigate tumor-initiating potential in gliomas and to advance the development of new therapies and diagnostics.
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http://dx.doi.org/10.1038/nmeth.1430 | DOI Listing |
Ann Med Surg (Lond)
December 2024
Medicine Faculty, University of Tübingen, Tübingen, Germany.
Background: This study investigates the gene expression characteristics of glioma-initiating cells (GIC), an important subgroup of glioblastoma (GBM), after knockdown of PBK (PDZ-binding kinase). Differentially expressed genes (DEGs) between PBK knockdown GIC and control groups were screened through bioinformatics methods. The authors analyzed the mechanisms and roles of these DEGs in GBM tumorigenesis and patient prognosis.
View Article and Find Full Text PDFComput Biol Med
August 2024
Department of Civil & Industrial Engineering, Industrial Analytics, Uppsala University, Sweden. Electronic address:
The CUSP9 protocol is a polypharmaceutical strategy aiming at addressing the complexity of glioblastoma by targeting multiple pathways. Although the rationale for this 9-drug cocktail is well-supported by theoretical and in vitro data, its effectiveness compared to its 511 possible subsets has not been comprehensively evaluated. Such an analysis could reveal if fewer drugs could achieve similar or better outcomes.
View Article and Find Full Text PDFBiochem Biophys Res Commun
April 2024
Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Japan; Genome Editing Innovation Center, Hiroshima University, Japan. Electronic address:
The elucidation of the properties of malignant glioma and development of therapeutic methods require glioblastoma-multiforme mice model with characteristics such as invasiveness, multinuclearity, and ability for mitosis. A previous study has shown that overexpression of active HRas (HRasL61) in neural stem/progenitor cells (NSCs) isolated from p53 knockout (KO) mice could induce glioma-initiating cells (GICs). The orthotopically transplantation of 10 cells into the forebrain of immunodeficient mice resulted in the development of glioblastoma multiforme-like malignant brain tumors.
View Article and Find Full Text PDFCancer Gene Ther
June 2024
Department of Chemical Engineering, University of Virginia, Charlottesville, VA, 22903, USA.
In glioblastoma, a mesenchymal phenotype is associated with especially poor patient outcomes. Various glioblastoma microenvironmental factors and therapeutic interventions are purported drivers of the mesenchymal transition, but the degree to which these cues promote the same mesenchymal transitions and the uniformity of those transitions, as defined by molecular subtyping systems, is unknown. Here, we investigate this question by analyzing publicly available patient data, surveying commonly measured transcripts for mesenchymal transitions in glioma-initiating cells (GIC), and performing next-generation RNA sequencing of GICs.
View Article and Find Full Text PDFJ Biol Chem
March 2024
Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Institute of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address:
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