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dc.contributor.authorYang, Ningen_US
dc.contributor.authorYan, Taoen_US
dc.contributor.authorZhu, Huaiyangen_US
dc.contributor.authorLiang, Xiaoen_US
dc.contributor.authorLeiss, Linaen_US
dc.contributor.authorSakariassen, Per Øysteinen_US
dc.contributor.authorSkaftnesmo, Kai Oveen_US
dc.contributor.authorHuang, Binen_US
dc.contributor.authorCostea, Daniela Elenaen_US
dc.contributor.authorEnger, Per Øyvinden_US
dc.contributor.authorLi, Xingangen_US
dc.contributor.authorWang, Jianen_US
dc.description.abstractBackground: Although several studies suggest that stromal fibroblasts mediate treatment resistance in several cancer types, little is known about how tumor-associated astrocytes modulate the treatment response in brain tumors. Since traditionally used metabolic assays do not distinguish metabolic activity between stromal and tumor cells, and since 2-dimensional co-culture system does not recreate the formidable complexity of the microenvironment within 3-dimensional structures such as solid tumor tissue, we instead established a glioblastoma (GBM) cell-specific bioluminescent assay for direct measurements of tumor cell viability in the treatment of clinical relevant drugs. Methods: Using lentiviral transfection, we established a panel of human GBM cell lines constitutively expressing a fusion transgene encoding luciferase and the enhanced green fluorescence protein (eGFP). We then initiated co-cultures with immortalized astrocytes, TNC-1, and the eGFP/Luc GBM cell lines. Next, we treated all eGFP/Luc GBM cell lines with Temozolomide (TMZ) or Doxorubicin, comparing co-cultures of glioblastoma (GBM) cells and TNC-1 astrocytes with mono-cultures of eGFP/Luc GBM cells. Cell viability was quantitated by measuring the luciferase expression. Results: Titration experiments demonstrated that luciferase expression was proportional to the number of eGFP/ Luc GBM cells, whereas it was not influenced by the number of TNC-1 cells present. Notably, the presence of TNC-1 astrocytes mediated significantly higher cell survival after TMZ treatment in the U251, C6, A172 cell lines as well as the in vivo propagated primary GBM tumor cell line (P3). Moreover, TNC-1 astrocytes mediated significantly higher survival after Doxorubicin treatment in the U251, and LN18 glioma cell lines. Conclusion: Glioma cell-specific bioluminescent assay is a reliable tool for assessment of cell viability in the brain tumor cell compartment following drug treatment. Moreover, we have applied this assay to demonstrate that astrocytes can modulate chemo sensitivity of GBM tumor cells. These effects varied both with the cell line and cytotoxic drug that were used, suggesting that several mechanisms may be involved.en_US
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.subjectBioluminescent assayeng
dc.subjectDrug resistanceeng
dc.titleA co-culture model with brain tumor-specific bioluminescence demonstrates astrocyte-induced drug resistance in glioblastomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2014 Yang et al.; licensee BioMed Central Ltd.
dc.rights.holderNing Yang et al.; licensee BioMed Central Ltd.
dc.source.journalJournal of Translational Medicine

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