Hypoxia promotes stem-like properties of laryngeal cancer cell lines by increasing the CD133+ stem cell fraction

Wu,Chun-Ping; Du,Huai-Dong; Gong,Hong-Li; Li,Da-Wei; Tao,Lei; Tian,Jie; Zhou,Liang

doi:10.3892/ijo.2014.2307

Hypoxia promotes stem-like properties of laryngeal cancer cell lines by increasing the CD133+ stem cell fraction

Authors:
- Chun-Ping Wu
- Huai-Dong Du
- Hong-Li Gong
- Da-Wei Li
- Lei Tao
- Jie Tian
- Liang Zhou
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China, Research Center, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China
Published online on: February 20, 2014 https://doi.org/10.3892/ijo.2014.2307
Pages: 1652-1660

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Abstract

Evidence indicates that a hypoxic microenvironment 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.

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