Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1

Yu Chih Chen, Charn Jung Chang, Han Shui Hsu, Yi Wei Chen, Lung Kuo Tai, Ling Ming Tseng, Guang-Yuh Chiou, Shih Ching Chang, Shou Yen Kao, Shih Hwa Chiou, Wen Liang Lo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)158-165
Number of pages8
JournalOral Oncology
Volume46
Issue number3
DOIs
StatePublished - 1 Mar 2010

Keywords

  • ALDH1
  • Bmi-1
  • Cancer stem cells
  • Head and neck squamous cell carcinoma (HNSCC)

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