Document Detail


Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1.
MedLine Citation:
PMID:  20036608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-29
Journal Detail:
Title:  Oral oncology     Volume:  46     ISSN:  1879-0593     ISO Abbreviation:  Oral Oncol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2011-03-31     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  158-65     Citation Subset:  IM    
Copyright Information:
(c) 2009 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aldehyde Dehydrogenase / genetics*
Animals
Carcinoma, Squamous Cell / genetics*,  pathology
Cell Line, Tumor
Female
Gene Knockdown Techniques
Head and Neck Neoplasms / genetics*,  pathology
Humans
Isoenzymes / genetics*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Retinal Dehydrogenase
Tumor Cells, Cultured
Tumor Markers, Biological / genetics*
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Tumor Markers, Biological; EC 1.2.1.-/aldehyde dehydrogenase 1; EC 1.2.1.3/Aldehyde Dehydrogenase; EC 1.2.1.36/Retinal Dehydrogenase

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