Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes

Molecular Cancer

Research

Lisa Bailey¹  Nandita Ganesh¹  Michael Gibson²  Michael Epperly²  Roberto Gomez-Casal²  Chitralekha Bhattacharya²  Vera Levina³  Per Basse⁴ 

[1] University of Pittsburgh Cancer Institute, 15213, Pittsburgh, PA, USA;University of Pittsburgh Cancer Institute, 15213, Pittsburgh, PA, USA;Department of Medicine, 15213, Pittsburg, PA, USA;University of Pittsburgh Cancer Institute, 15213, Pittsburgh, PA, USA;Department of Medicine, 15213, Pittsburg, PA, USA;University of Pittsburgh Cancer Institute, Hillman Cancer Center, Rm. 1.19c, 5117 Center Ave, 15213, Pittsburgh, PA, USA;University of Pittsburgh Cancer Institute, 15213, Pittsburgh, PA, USA;Departments of Pathology, University of Pittsburgh, 15213, Pittsburgh, PA, USA;

关键词: Non-small cell lung cancer;    Ionizing radiation;    Cancer stem cell;    Epithelial-mesenchymal transition;   

DOI  :  10.1186/1476-4598-12-94

 received in 2013-04-03, accepted in 2013-08-14,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Gomez-casal et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.