caa a22 4500 44579531X CHVBK 20180317145123.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s10620-010-1340-0 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1340-0 Pancreatic Cancer Cells Resistant to Chemoradiotherapy Rich in "Stem-Cell-Like” Tumor Cells [Elektronische Daten] [Zhiyong Du, Renyi Qin, Cuifeng Wei, Min Wang, Chengjian Shi, Rui Tian, Chenghong Peng] Background: Tumor resistance to chemoradiation therapy is partly attributed to the presence of apoptosis-resistant cancer stem cells (CSCs). Chemoradiation therapy can enrich CSCs by killing apoptosis-susceptible cancer cells. Aim: Our preliminary study showed chemoradiation-resistant pancreatic cancer cells to have some CSC characteristics, and to undergo epithelial-mesenchymal transition (EMT); we aimed to verify that study's implication that chemoradiation-resistant subpopulations are enriched with "stem-cell-like” tumor cells, which may be linked to EMT. Methods: Four pancreatic cancer cell lines were cultured in gemcitabine with synchronous radiotherapy to obtain resistant subpopulations. Morphological changes were observed under microscope; migration and invasiveness were assessed by Transwell tests. Protein expression was determined by immunoblotting. Pancreatic CSC markers were studied using fluorescence-activated cell sorting analyses. Colony-formation tests, tumor sphere formation assays, and tumor xenografts in BALB/C nude mice were used to evaluate "stemness” in resistant cells. Results: Resistant cells expressed more antiapoptotic protein Bcl-2, apoptosis-inhibitory protein survivin, and stem cell markers Oct4, ABCG2, CD24, and CD133, were more tumorigenic invitro and invivo, and showed phenotypic and molecular changes consistent with EMT, including upregulation of vimentin and downregulation of E-cadherin. They were also more invasive and migratory. Conclusions: We found chemoradiation-resistant pancreatic cancer cells to be similar to CSCs and to undergo EMT, suggesting that chemoradiation resistance-induced EMT is linked to CSC generation. Springer Science+Business Media, LLC, 2010 Pancreatic cancer nationallicence Cancer stem cells nationallicence Radioresistance nationallicence Chemoresistance nationallicence Epithelial-mesenchymal transition nationallicence Du Zhiyong Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University Medical School, 200025, Shanghai, People's Republic of China aut Qin Renyi Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Wei Cuifeng Department of Endocrinology, Jingmen First Hospital, 448000, Jingmen, People's Republic of China aut Wang Min Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Shi Chengjian Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Tian Rui Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Peng Chenghong Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University Medical School, 200025, Shanghai, People's Republic of China aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/3(2011-03-01), 741-750 0163-2116 56:3<741 2011 56 10620 https://doi.org/10.1007/s10620-010-1340-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1340-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Du Zhiyong Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University Medical School, 200025, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Qin Renyi Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Wei Cuifeng Department of Endocrinology, Jingmen First Hospital, 448000, Jingmen, People's Republic of China aut NATIONALLICENCE 700 1- Wang Min Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Shi Chengjian Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Tian Rui Department of Pancreatic-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Peng Chenghong Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University Medical School, 200025, Shanghai, People's Republic of China aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/3(2011-03-01), 741-750 0163-2116 56:3<741 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer