Radiotherapy diagnostic biomarkers in radioresistant human H460 lung cancer stem-like cellsopen access
- Authors
- Yun H.S.[Yun H.S.]; Baek J.-H.[Baek J.-H.]; Yim J.-H.[Yim J.-H.]; Um H.-D.[Um H.-D.]; Park J.K.[Park J.K.]; Song J.-Y.[Song J.-Y.]; Park I.-C.[Park I.-C.]; Kim J.-S.[Kim J.-S.]; Lee S.-J.[Lee S.-J.]; Lee C.-W.[Lee C.-W.]; Hwang S.-G.[Hwang S.-G.]
- Issue Date
- 2016
- Publisher
- TAYLOR & FRANCIS INC
- Keywords
- Biomarker; cancer stem-like cells; diagnose; H460 lung cancer cells; proteomics; radioresistance; radiotherapy
- Citation
- CANCER BIOLOGY & THERAPY, v.17, no.2, pp.208 - 218
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCER BIOLOGY & THERAPY
- Volume
- 17
- Number
- 2
- Start Page
- 208
- End Page
- 218
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/41727
- DOI
- 10.1080/15384047.2016.1139232
- ISSN
- 1538-4047
- 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 thesePAI-2, NOMO2, KLC4, and PLOD3have 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.
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