4.7 Article

CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma

Journal

BRITISH JOURNAL OF CANCER
Volume 111, Issue 3, Pages 506-514

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.289

Keywords

CD10; head and neck squamous cell carcinoma; cell surface antigen array; chemo-resistance; radio-resistance; cancer stem cells

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology, Japan
  2. Ministry of Health, Labour and Welfare, Japan
  3. Kobayashi Cancer Research Foundation
  4. Princess Takamatsu Cancer Research Fund, Japan
  5. SENSHIN Medical Research Foundation, Japan
  6. National Institute of Biomedical Innovation, Japan

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Background: Cancer stem cells (CSCs) are responsible for treatment failure. However, their identification and roles in resistance are not well established in head and neck squamous cell carcinoma (HNSCC). Methods: Three HNSCC cell lines (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell surface antigens were analysed by LyoPlate, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. Results: CD10, CD15s, CD146 and CD282 were upregulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. Isolation mediated by FACS revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. Conclusions: CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory HNSCC.

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