title: Hypoxia promotes stem-like properties of laryngeal cancer cell lines by increasing the CD133+ stem cell fraction.
abstract: Evidence indicates that a hypoxic micro-environment plays an essential role in the regulation of cancer stem cells (CSCs). However, whether hypoxia is able to regulate the stem-like biological properties of laryngeal cancer cells remains unknown. In this study, we investigated the influence of hypoxia on the stemness of two laryngeal cancer cell lines, Hep-2 and AMC-HN-8. We cultured the two cell lines under hypoxia and normoxia and examined the influence of hypoxia on the expression of hypoxia-inducible factors (HIFs) and the cancer stem-like properties of these cells, including cell cycle distribution, expression of stem cell genes (OCT4, SOX2 and NANOG) and laryngeal CSC surface marker (CD133), proliferation, invasion, colony formation and sphere formation capacity. We determined that both of these cell lines, when maintained under hypoxic conditions, showed expanded cells in the G0/G1 phase, exhibited preferential expression of stem cell genes and CD133, and manifested upregulation of HIFs. When treated with hypoxia followed by normoxia exposure, the two cell lines exhibited enhanced capacities for proliferation, invasion, and sphere and colony formation compared with cells maintained consistently under normoxia. Our findings indicate that a hypoxic microenvironment may upgrade the stem-like biological properties of laryngeal cancer cell lines by the expansion of the CD133(+) stem cell fraction.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Du
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Gong
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Research Center, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides