title: IL-6 promotes growth and epithelial-mesenchymal transition of CD133+ cells of non-small cell lung cancer.
abstract: We examined IL-6 effects on growth, epithelial-mesenchymal transition (EMT) process, and metastatic ability of CD133+ and CD133- cell subpopulations isolated from three non-small cell lung cancer (NSCLC) cell lines: A549, H157, and H1299. We developed IL-6 knocked-down and scramble (sc) control cells of A549 and H157 cell lines by lentiviral infection system, isolated CD133+ and CD133- sub-populations, and investigated the IL-6 role in self-renewal/growth of these cells. IL-6 showed either an inhibitory or lack of effect in modulating growth of CD133- cells depending on intracellular IL-6 levels, but there was higher self-renewal ability of IL-6 expressing CD133+ cells than IL-6 knocked down cells, confirming the promoter role of IL-6 in CD133+ cells growth. We then examined tumor growth of xenografts developed from CD133+ cells of A549IL-6si vs. A549sc cell lines. Consistently, there was retarded growth of tumors developed from A549IL-6si, CD133+ cells compared to tumors originating from A549sc, CD133+ cells. The effect of IL-6 in promoting CD133+ self-renewal was due to hedgehog (Hhg) and Erk signaling pathway activation and higher Bcl-2/Bcl-xL expression. We also investigated whether IL-6 regulates the EMT process of CD133- and CD133+ cells differently. Expression of the EMT/metastasis-associated molecules in IL-6 expressing cells was higher than in IL-6 knocked down cells. Together, we demonstrated dual roles of IL-6 in regulating growth of CD133- and CD133+ subpopulations of lung cancer cells and significant regulation of IL-6 on EMT/metastasis increase in CD133+ cells, not in CD133- cells.
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Shanzhou
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tsai
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Strojny
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Keng
authors.affiliation: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Yuhchyau
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015850:Interleukin-6; C000606023:PROM1 protein, human; D012333:RNA, Messenger
keywords: CD133+; IL-6; cancer stem cells; non-small cell lung cancer; self-renewal