Physiologic Oxygen Concentration Enhances the Stem-Like Properties of CD133(+) Human Glioblastoma Cells In vitro

Moffitt Cancer Center, Tampa, FL 33612, USA.
Molecular Cancer Research (Impact Factor: 4.38). 05/2009; 7(4):489-97. DOI: 10.1158/1541-7786.MCR-08-0360
Source: PubMed


In vitro investigations of tumor stem-like cells (TSC) isolated from human glioblastoma (GB) surgical specimens have been done primarily at an atmospheric oxygen level of 20%. To determine whether an oxygen level more consistent with in situ conditions affects their stem cell-like characteristics, we compared GB TSCs grown under conditions of 20% and 7% oxygen. Growing CD133(+) cells sorted from three GB neurosphere cultures at 7% O(2) reduced their doubling time and increased the self-renewal potential as reflected by clonogenicity. Furthermore, at 7% oxygen, the cultures exhibited an enhanced capacity to differentiate along both the glial and neuronal pathways. As compared with 20%, growth at 7% oxygen resulted in an increase in the expression levels of the neural stem cell markers CD133 and nestin as well as the stem cell markers Oct4 and Sox2. In addition, whereas hypoxia inducible factor 1alpha was not affected in CD133(+) TSCs grown at 7% O(2), hypoxia-inducible factor 2alpha was expressed at higher levels as compared with 20% oxygen. Gene expression profiles generated by microarray analysis revealed that reducing oxygen level to 7% resulted in the up-regulation and down-regulation of a significant number of genes, with more than 140 being commonly affected among the three CD133(+) cultures. Furthermore, Gene Ontology categories up-regulated at 7% oxygen included those associated with stem cells or GB TSCs. Thus, the data presented indicate that growth at the more physiologically relevant oxygen level of 7% enhances the stem cell-like phenotype of CD133(+) GB cells.

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Available from: Muhammad Jamal, Oct 13, 2015
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    • "The hypoxic and fibrogenic microenvironment of PDAC comprises not only tumor cells but also surrounding stromal cells, such as stellate, endothelial, and infiltrating immune cells. Researchers demonstrated that hypoxic conditions resulted in a large increase in the expression of the neural stem cell markers CD133 and Nestin as well as the stem cell markers Oct4 and Sox2 [121]. Hypoxia also induced the human embryonic stem cell transcriptional program, including the induced pluripotent stem cell inducers Oct4, Nanog, Sox2, KLF4, c-Myc, and microRNA302, in 11 cancer cell lines [122]. "
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    Molecular Cancer 12/2013; 12(1):159. DOI:10.1186/1476-4598-12-159 · 4.26 Impact Factor
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    • "A hypoxic environment is also a GSC niche that maintains their self-renewal [67, 68]. Hypoxia promotes expansion of the GSC fraction and regulates the expression of stem cell markers [69, 70]. Hypoxic conditions induce VEGF expression in both GSCs and non-GSCs, but the VEGF levels are consistently higher in GSCs [68]. "
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    05/2013; 2013(3):673793. DOI:10.1155/2013/673793
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    • "The NSC11 and GBAM1 CD133+ GSC cultures used in these studies met the criteria for tumor stem-like cells [4] including self-renewal, differentiation along glial and neuronal pathways, expression of stem cell related genes and formation of brain tumors when implanted in immunodeficient mice [13], [14]. To induce differentiation of the GSC lines, cells were exposed to DMEM/F-12 containing 10% FBS for 10 days, which resulted in the loss of CD133 expression, the gain of expression of GFAP and/or β-III tubulin and cell cycle arrest. "
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