Research Papers:

Cancer stem cell related markers of radioresistance in head and neck squamous cell carcinoma

Ina Kurth _, Linda Hein, Katrin Mäbert, Claudia Peitzsch, Lydia Koi, Monica Cojoc, Leoni Kunz-Schughart, Michael Baumann and Anna Dubrovska

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Oncotarget. 2015; 6:34494-34509. https://doi.org/10.18632/oncotarget.5417

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Ina Kurth1, Linda Hein1, Katrin Mäbert1, Claudia Peitzsch1, Lydia Koi2, Monica Cojoc1, Leoni Kunz-Schughart1, Michael Baumann1,2,3,4,5, Anna Dubrovska1,4,5

1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

2Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

3Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology, Dresden, Germany

4German Cancer Consortium (DKTK), Dresden, Germany

5German Cancer Research Center (DKFZ), Heidelberg, Germany

Correspondence to:

Anna Dubrovska, e-mail: [email protected]

Ina Kurth, e-mail: [email protected]

Keywords: cancer stem cells, radioresistance, aldehyde dehydrogenase, head and neck squamous cell carcinoma (HNSCC)

Received: June 02, 2015     Accepted: September 25, 2015     Published: October 07, 2015


Despite recent advances in understanding of the molecular pathogenesis and improvement of treatment techniques, locally advanced head and neck squamous cell carcinoma (HNSCC) remains associated with an unfavorable prognosis. Compelling evidence suggests that cancer stem cells (CSC) may cause tumor recurrence if they are not eradicated by current therapies as radiotherapy or radio-chemotherapy. Recent in vitro studies have demonstrated that CSCs may be protected from treatment-induced death by multiple intrinsic and extrinsic mechanisms. Therefore, early determination of CSC abundance in tumor biopsies prior-treatment and development of therapeutics, which specifically target CSCs, are promising strategies to optimize treatment. Here we provide evidence that aldehyde dehydrogenase (ALDH) activity is indicative for radioresistant HNSCC CSCs. Our study suggests that ALDH+ cells comprise a population that maintains its tumorigenic properties in vivo after irradiation and may provide tumor regrowth after therapy. We found that ALDH activity in HNSCC cells can be attributed, at least in part, to the ALDH1A3 isoform and inhibition of the ALDH1A3 expression by small interfering RNA (siRNA) decreases tumor cell radioresistance. The expression dynamic of ALDH1A3 upon irradiation by either induction or selection of the ALDH1A3 positive population correlates to in vivo curability, suggesting that changes in protein expression during radiotherapy are indicative for tumor radioresistance. Our data indicate that ALDH1A3+ HNSCC cells may contribute to tumor relapse after irradiation, and inhibition of this cell population might improve therapeutic response to radiotherapy.

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