Journal
ORAL ONCOLOGY
Volume 46, Issue 3, Pages 158-165Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.oraloncology.2009.11.007
Keywords
Head and neck squamous cell carcinoma (HNSCC); ALDH1; Bmi-1; Cancer stem cells
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Funding
- National Science Council [NSC-97-3111-B-075-001-MY3/98-2314-B-075008-MY3]
- Taipei Veterans General Hospital [V97B1-006/E1-008/F-001/F-004/F-010]
- National Yang-Ming University [98-EC-17-A-19-S2-0107]
- Department of Industrial Technology, Ministry of Economic Affairs, Taiwan
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Bmi-1, a member of the Polycomb family of transcriptional repressors, is essential for maintaining the self-renewal abilities of adult stem cells. Bmi-1 has been demonstrated to play a role in tumorigenesis in head and neck squamous cell carcinomas (HNSCCs). A recent study has further suggested that ALDH1 may be considered to be a putative marker for HNSCC-derived cancer stem cells. However, the role that Bmi-1 plays in HNSCC-derived ALDH1-positive cells (HNSCC-ALDH1(+)) has yet to be determined. In this study, we demonstrated that HNSCC-ALDH1(+) cells possess tumor initiating properties, are capable of self-renewal, and express higher levels of Bmi-1 as compared to HNSCC-ALDH1(+) cells. To further explore the functional role of Bmi-1 in HNSCC-ALDH1(+) cells, we used a lentiviral vector expressing shRNA to knock down Bmi-1 expression (sh-Bmi-1) in HNSCC-ALDH1(+) cells. Silencing of Bmi-1 significantly enhanced the sensitivity of HNSCC-ALDH1(+) cells to chemoradiation and increased the degree of chemoradiation-mediated apoptosis that occurred. Importantly, knockdown of Bmi-1 increased the effectiveness of radiotherapy and led to the inhibition of tumor growth in nude mice transplanted with HNSCC-ALDH1(+) cells. Kaplan-Meier survival analysis indicated that the mean survival rate of HNSCC-ALDH1(+) tumor-bearing immunocompromised mice treated with radiotherapy was significantly improved by treatment with sh-Bmi-1 as well. In summary, these results suggest that Bmi-1 is a potential target for increasing the sensitivity of HNSCC cancer stem cells to chemoradiotherapy. (C) 2009 Elsevier Ltd. All rights reserved.
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