Hypoxia-induced cell stemness leads to drug resistance and poor prognosis in lung adenocarcinoma

Background: Since cancer stem cells exhibit embryonic-like self-renewal characteristics and malignant behavior, including drug resistance and metastasis, they may be the origin of tumorigenesis and cancer recurrence. Cancer cell sternness is also highly relevant to cancer in hypoxic environments. Methods: In our study, we used cobalt dichloride (CoCl2) to create a hypoxic environment for lung adenocarcinoma A549 cells and the cisplatine-resistant cell line A549/DDP. The cancer stem-like CD166 positive population and the cells' sternness were detected by flowcytometry and quantitative real-time PCR after separation using magnetic antibodies. Drug resistance to cisplatine, docetaxel and pemetrexed was also measured. Finally, a tissue array was used to analyze the relationship between hypoxia-induced stemness and overall survival after radical surgery. Results: Data showed that chemical-induced hypoxia changed cell sternness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stern cell-like population showed greater drug resistance than the CD166-negative cells. Tissue array studies also suggested a poorer prognosis for patients whose tissue expressed higher CD166 levels. Conclusion: Our findings indicate that chemical hypoxia may augment cancer cell sternness and drug resistance in CD166-positive stern cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.