Mingchuan Zhao1, Yishi Zhang2, Huijun Zhang3, Shaohua Wang3, Mengmeng Zhang4, Xi Chen5, Heyong Wang6, Gang Zeng7, Xiaofeng Chen8, Gentao Liu9, Caicun Zhou1. 1. Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. 2. Department of Oncology, Fuda Hospital, School of Medicine, Jinan University, Guangzhou, China. 3. Department of Thoracic Surgery, Huashan Hospital, School of Medicine, Fudan University, Shanghai, China. 4. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. 5. Center for Translational Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. 6. Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. 7. Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 8. Department of Thoracic Surgery, Huashan Hospital, School of Medicine, Fudan University, Shanghai, China. Electronic address: cxf3166@126.com. 9. Center for Translational Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: liugt2000@gmail.com.
Abstract
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 stemness 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' stemness 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 stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stem 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 stemness and drug resistance in CD166-positive stem cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer.
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 stemness 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' stemness 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 stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stem 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 stemness and drug resistance in CD166-positive stem cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer.
Authors: Yuyi Wang; Ming Jiang; Zhixi Li; Jiantao Wang; Chi Du; Liu Yanyang; Yang Yu; Xia Wang; Nan Zhang; Maoyuan Zhao; Li Wang; Mei Li; Feng Luo Journal: Cell Biosci Date: 2015-12-23 Impact factor: 7.133