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首页> 外文期刊>Molecular Cancer >Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes
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Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes

机译：非小细胞肺癌细胞在电离辐射治疗中存活下来，显示出癌症干细胞和上皮-间质转化表型

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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 .
机译：电离辐射（IR）用于诊断为不可切除的非小细胞肺癌（NSCLC）的患者，但是由于放射抵抗，放射治疗仍在很大程度上姑息治疗。癌症干细胞（CSC）以及上皮-间质转化（EMT）可能有助于实体瘤的耐药性和放射抗性机制。在这里，我们研究了A549和H460 NSCLC细胞的分子表型，这些细胞在用IR（5Gy）处理后仍存活下来，并以漂浮的肿瘤球和细胞的形式生长，并在辐照后保持在单层。一周后收集未辐照和辐照的细胞，接种到超低附着平板上，并以肿瘤球的形式繁殖。幸存下来并在球体中生长的大块NSCLC细胞表达癌症干细胞表面和胚胎干细胞标志物，并且能够自我更新并产生分化的后代。这些细胞也具有间充质表型。特别是，辐射幸存的球形细胞表达的CSC标记（CD24和CD44），核β-连环蛋白和EMT标记（Snail1，波形蛋白和N-钙粘蛋白）的水平明显高于未辐照的肺肿瘤球形细胞。在辐照后单层维持的H460细胞中检测到Oct-4，Sox2和β-连环蛋白的上调水平，但在辐射中未存活的贴壁A459细胞。在A549和H460细胞系中，放射存活的球形细胞和放射存活的贴壁细胞中的PDGFR-β均上调。将IR治疗与具有抗PDFGR活性的抑制剂axitinib或dasatinib结合使用，可增强NSCLC放射疗法的体外疗效。我们的发现表明，放射存活的细胞具有结合CSCs和EMT特性的复杂表型。 CD44，SNAIL和PDGFR-β在放射存活的细胞中显着上调，可能被认为是NSCLC放射治疗反应的标志物。

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