title: Radiotherapy diagnostic biomarkers in radioresistant human H460 lung cancer stem-like cells.
abstract: Tumor cell radioresistance is a major contributor to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. In this work, we established a radioresistant H460 (RR-H460) cell line from parental radiosensitive H460 lung cancer cells by exposure to fractionated radiation. The radiation-resistant, anti-apoptotic phenotype of RR-H460 cell lines was confirmed by their enhanced clonogenic survival and increased expression of the radioresistance genes Hsp90 and Her-3. RR-H460 cells displayed characteristics of cancer stem-like cells (CSCs), including induction of the surface marker CD44 and stem cell markers Nanog, Oct4, and Sox2. RR-H460 cells also exhibited sphere formation and malignant behavior, further supporting a CSC phenotype. Using proteomic analyses, we identified 8 proteins that were up-regulated in RR-H460 CSC lines and therefore potentially involved in radioresistance and CSC-related biological processes. Notably, 4 of these-PAI-2, NOMO2, KLC4, and PLOD3-have not been previously linked to radioresistance. Depletion of these individual genes sensitized RR-H460 cells to radiotoxicity and additively enhancing radiation-induced apoptosis. Our findings suggest the possibility of integrating molecular targeted therapy with radiotherapy as a strategy for resolving the radioresistance of lung tumors.
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.|b Department of Life Science , College of Natural Sciences, Hanyang University , Seoul , South Korea.
authors.forename: Hong Shik
authors.initials: HS
authors.lastname: Yun
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.|c Department of Molecular Cell Biology , Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine , Suwon , South Korea.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Baek
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yim
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Park
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: c Department of Molecular Cell Biology , Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine , Suwon , South Korea.
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: a Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul , South Korea.
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects; D040901:Proteomics; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Biomarker; H460 lung cancer cells; cancer stem-like cells; diagnose; proteomics; radioresistance; radiotherapy