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Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer |
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| Authors: | Yu-Chih Chen Yi-Wei Chen Han-Shui Hsu Ling-Ming Tseng Pin-I Huang Kai-Hsi Lu Dow-Tien Chen Lung-Kuo Tai Ming-Chi Yung Shih-Ching Chang Hung-Hai Ku Shih-Hwa Chiou Wen-Liang Lo |
| Affiliation: | a Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taiwan b Institute of Anatomy & Cell Biology, National Yang-Ming University, Taiwan c Department of Dentistry, National Yang-Ming University, No. 155, Sec. 2, Linong St., Taipei city 11221, Taiwan d Cancer Center, Taipei Veterans General Hospital, Taiwan e Department of Surgery, Taipei Veterans General Hospital, Taiwan f Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan g Division of Oral and Maxillofacial Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei city 11217, Taiwan h Department of Medical Education and Research, Department of Cardiovascular Surgery, Zhongxiao Branch, Taipei City Hospital, No. 87, Tongde Rd., Taipei city 11556, Taiwan |
| Abstract: | Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stem cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1+ cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1+-lineage cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stem-like properties, and blocked the tumorigenic abilities of CD44+CD24−ALDH1+ cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1+ could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC. |
| Keywords: | Aldehyde dehydrogenase 1 Cancer stem cell Head and neck squamous cancer |
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