title: High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells.
abstract: Hypoxia-inducible factor-2 alpha (HIF-2α) has been shown to regulate cell stemness, although the expression and effects of HIF-2α in lung cancer stem cells remained unclear. This study investigated HIF-2α expression in lung cancer stem cells, as well as the relationship between HIF-2α expression and radioresistance in lung cancer cells. Stem-like cells (CD133(+)) in the non-small-cell lung cancer cell line A549 were enriched by serum-free culture conditions, and CD133(+) cells were sorted via fluorescence-activated cell sorting. A549 cells were treated with middle-infrared radiation, and the level of HIF-2α expression was determined by a quantitative polymerase chain reaction assay and western blot analysis. The level of HIF-2α expression in tissue sections from 50 cases of clinically confirmed non-small-cell lung cancer was determined via immunohistochemical analysis, and its correlation with prognosis after radiotherapy was analyzed. HIF-2α levels in CD133(+) cells were significantly higher than those in CD133(-) cells (P = 0.032). However, after radiation treatment, these levels were significantly upregulated in both CD133(+) and CD133(-) cells (P = 0.031 and P = 0.023, respectively). After irradiation, the proportions of apoptotic, dead, and autophagic CD133(+) A549 cells were considerably lower than those of CD133(-) A549 cells (P < 0.05). Furthermore, the recovery of carcinoembryonic antigen to pre-radiation levels was more rapid in lung cancer patients with high levels of HIF-2α expression, and these patients had shorter survival times (P = 0.018). HIF-2α is highly expressed in lung cancer stem cells, which may lead to radioresistance. In conclusion, HIF-2α is a potential prognostic marker for lung cancer.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: J C
authors.initials: JC
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: M H
authors.initials: MH
authors.lastname: Wan
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: D L
authors.initials: DL
authors.lastname: Niu
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis / Q000528:radiation effects; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000528:radiation effects; D010455:Peptides / Q000235:genetics; D011379:Prognosis; D011836:Radiation Tolerance / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D010455:Peptides; D000099162:Endothelial PAS Domain-Containing Protein 1; C000606023:PROM1 protein, human