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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Pages (from-to)34494-34509
Number of pages16
JournalOncotarget
Volume6
Issue number33
Publication statusPublished - 27 Oct 2015
Peer-reviewedYes

External IDs

Scopus 84946551205
researchoutputwizard legacy.publication#67941
PubMed 26460734
PubMedCentral PMC4741468

Keywords

Sustainable Development Goals

Keywords

  • Aldehyde Oxidoreductases/metabolism, Animals, Biomarkers, Tumor/analysis, Blotting, Western, Carcinoma, Squamous Cell/enzymology, Cell Line, Tumor, Flow Cytometry, Fluorescent Antibody Technique, Gene Knockdown Techniques, Head and Neck Neoplasms/enzymology, Humans, Mice, Mice, Nude, Neoplastic Stem Cells/enzymology, Radiation Tolerance/physiology, Reverse Transcriptase Polymerase Chain Reaction, Squamous Cell Carcinoma of Head and Neck, Tissue Array Analysis, Xenograft Model Antitumor Assays