Isolation of head and neck squamous carcinoma cancer stem-like cells in a syngeneic mouse model and analysis of hypoxia effect

Duarte,Sónia; Loubat,Agnès; Momier,David; Topi,Majlinda; Faneca,Henrique; Pedroso de Lima,Maria   C.; Carle,Georges  F.; Pierrefite-Carle,Valérie

doi:10.3892/or.2012.1904

September 2012 Volume 28 Issue 3

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September 2012 Volume 28 Issue 3

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Article

Isolation of head and neck squamous carcinoma cancer stem-like cells in a syngeneic mouse model and analysis of hypoxia effect

Authors:
- Sónia Duarte
- Agnès Loubat
- David Momier
- Majlinda Topi
- Henrique Faneca
- Maria C. Pedroso de Lima
- Georges F. Carle
- Valérie Pierrefite-Carle
View Affiliations / Copyright

Affiliations: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal, IFR50, School of Medicine, University of Nice Sophia Antipolis, Nice, France, GéPITOs UMR 6235 CNRS, School of Medicine, University of Nice Sophia Antipolis, Nice, France
Pages: 1057-1062
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Published online on: July 6, 2012

https://doi.org/10.3892/or.2012.1904
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Abstract

The incidence of oral tumors is increasing around the world and despite recent advances in early detection and diagnosis, current treatments are still unsatisfactory. Recent data suggest that tumor persistence and recurrence could be due to the presence of a rare cell population called cancer stem cells (CSCs), which are generally spared by traditional treatments. Therefore, identification and characterization of CSCs are extremely important to develop novel and effective treatment strategies for cancer. The aim of this study was to identify and isolate CSCs in an established murine head and neck squamous cell carcinoma (HNSCC) cell line and to investigate the influence of hypoxic conditions on the isolated cell population. Using the expression of the aldehyde dehydrogenase 1 (ALDH1) enzymatic activity, which is now recognized as a CSC marker in various tumors, we isolated a cell population expressing high levels of ALDH1 (ALDH1high) representing 1±0.6% in the murine SCC-VII cell line. These cells were injected subcutaneously in syngeneic animals to evaluate their tumorigenic properties. For the lowest injected cell dose (250 injected cells), tumor occurrence and median tumor size were higher in ALDH1high injected mice than in ALDH1low injected mice. Following an in vivo passage and culture in serum-free medium, the percentage of ALDH1high cells increased by 3‑fold in SCC-VII CSCs (oral spheres) compared to the SCC-VII cell line. This percentage was further increased when oral spheres were cultured under hypoxic conditions. In conclusion, this study reports for the first time the isolation of HNSCC CSCs in a syngeneic mouse model and the use of hypoxia as a method to further enrich the ALDH1high cell population.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Isolation of head and neck squamous carcinoma cancer stem-like cells in a syngeneic mouse model and analysis of hypoxia effect

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