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Keywords {🔍}

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Topics {✒️}

small-cell lung cancer small-cell lung cancer basic helix-loop-helix cancer stem/progenitor cells open access article cancer-initiating cell profit article download pdf plastic 10 μl-pipette tip vascular-mesenchymal cross-talk e-cadherin/beta-catenin complex modulating epithelial-mesenchymal transition stem-cell selective conditions ionizing radiation induced article gomez-casal hypoxia-inducible factor-1alpha 137cs gamma-ray source epithelial-mesenchymal transition phenotypes radiation–survived cells growing cell-surface glycoprotein involved serum-free media supplemented tumor-sphere forming cells predicting disease-free survival ir-survived sphere cells multitargeted anti-angiogenic agents cadherin/β-catenin complex stromal derived factor cancer stem cell de jong jm ir-treated adherent cells wound healing assay lung cancer cases full size image lung sphere cells stem cell traits cancer stem cells anti-pdgfr beta activity radiation survived cells mesenchymal stem cell cell stem cell transcription factors including snail ultra-low attachment plates arrayscan hcs reader autocrine signals induce tumor sphere growth breast cancer cells epithelial-mesenchymal transition tumor stem cell human pancreatic cancer privacy choices/manage cookies nature cell biology

Questions {❓}

• Gupta PB, Chaffer CL, Weinberg RA: Cancer stem cells: mirage or reality?
• Kong D, Li Y, Wang Z, Sarkar FH: Cancer stem cells and epithelial-to-mesenchymal transition (EMT)-phenotypic cells: are they cousins or twins?
• Zoller M: CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?

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         headline:Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes
         description:Ionizing radiation (IR) is used for patients diagnosed with unresectable non small cell lung cancer (NSCLC), however radiotherapy remains largely palliative due to radioresistance. Cancer stem cells (CSCs), as well as epithelial-mesenchymal transition (EMT), may contribute to drug and radiation resistance mechanisms in solid tumors. Here we investigated the molecular phenotype of A549 and H460 NSCLC cells that survived treatment with IR (5Gy) and are growing as floating tumor spheres and cells that are maintained in a monolayer after irradiation. Non-irradiated and irradiated cells were collected after one week, seeded onto ultra low attachment plates and propagated as tumor spheres. Bulk NSCLC cells which survived radiation and grew in spheres express cancer stem cell surface and embryonic stem cell markers and are able to self-renew, and generate differentiated progeny. These cells also have a mesenchymal phenotype. Particularly, the radiation survived sphere cells express significantly higher levels of CSC markers (CD24 and CD44), nuclear β-catenin and EMT markers (Snail1, Vimentin, and N-cadherin) than non-irradiated lung tumor sphere cells. Upregulated levels of Oct-4, Sox2 and beta-catenin were detected in H460 cells maintained in a monolayer after irradiation, but not in radiation survived adherent A459 cells. PDGFR-beta was upregulated in radiation survived sphere cells and in radiation survived adherent cells in both A549 and H460 cell lines. Combining IR treatment with axitinib or dasatinib, inhibitors with anti-PDFGR activity, potentiates the efficacy of NSCLC radiotherapy in vitro. Our findings suggest that radiation survived cells have a complex phenotype combining the properties of CSCs and EMT. CD44, SNAIL and PDGFR-beta are dramatically upregulated in radiation survived cells and might be considered as markers of radiotherapy response in NSCLC.
         datePublished:2013-08-16T00:00:00Z
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            Non-small cell lung cancer
            Ionizing radiation
            Cancer stem cell
            Epithelial-mesenchymal transition
            Cancer Research
            Oncology
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      headline:Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes
      description:Ionizing radiation (IR) is used for patients diagnosed with unresectable non small cell lung cancer (NSCLC), however radiotherapy remains largely palliative due to radioresistance. Cancer stem cells (CSCs), as well as epithelial-mesenchymal transition (EMT), may contribute to drug and radiation resistance mechanisms in solid tumors. Here we investigated the molecular phenotype of A549 and H460 NSCLC cells that survived treatment with IR (5Gy) and are growing as floating tumor spheres and cells that are maintained in a monolayer after irradiation. Non-irradiated and irradiated cells were collected after one week, seeded onto ultra low attachment plates and propagated as tumor spheres. Bulk NSCLC cells which survived radiation and grew in spheres express cancer stem cell surface and embryonic stem cell markers and are able to self-renew, and generate differentiated progeny. These cells also have a mesenchymal phenotype. Particularly, the radiation survived sphere cells express significantly higher levels of CSC markers (CD24 and CD44), nuclear β-catenin and EMT markers (Snail1, Vimentin, and N-cadherin) than non-irradiated lung tumor sphere cells. Upregulated levels of Oct-4, Sox2 and beta-catenin were detected in H460 cells maintained in a monolayer after irradiation, but not in radiation survived adherent A459 cells. PDGFR-beta was upregulated in radiation survived sphere cells and in radiation survived adherent cells in both A549 and H460 cell lines. Combining IR treatment with axitinib or dasatinib, inhibitors with anti-PDFGR activity, potentiates the efficacy of NSCLC radiotherapy in vitro. Our findings suggest that radiation survived cells have a complex phenotype combining the properties of CSCs and EMT. CD44, SNAIL and PDGFR-beta are dramatically upregulated in radiation survived cells and might be considered as markers of radiotherapy response in NSCLC.
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      dateModified:2013-08-16T00:00:00Z
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         Non-small cell lung cancer
         Ionizing radiation
         Cancer stem cell
         Epithelial-mesenchymal transition
         Cancer Research
         Oncology
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