Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1
Autor: | Yu Chih Chen, Yi Wei Chen, Ling Ming Tseng, Guang-Yuh Chiou, Wen Liang Lo, Shih Ching Chang, Shou Yen Kao, Lung Kuo Tai, Shih Hwa Chiou, Han Shui Hsu, Charn Jung Chang |
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Rok vydání: | 2010 |
Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Cell Mice Nude medicine.disease_cause Aldehyde Dehydrogenase 1 Family Mice stomatognathic system Cancer stem cell Cell Line Tumor Biomarkers Tumor Tumor Cells Cultured otorhinolaryngologic diseases medicine Animals Humans Aged Mice Inbred BALB C business.industry Retinal Dehydrogenase Cancer Aldehyde Dehydrogenase Middle Aged medicine.disease Head and neck squamous-cell carcinoma Isoenzymes stomatognathic diseases medicine.anatomical_structure Oncology Head and Neck Neoplasms Apoptosis Gene Knockdown Techniques Carcinoma Squamous Cell Cancer research Female Oral Surgery Stem cell business Carcinogenesis Adult stem cell |
Zdroj: | Oral Oncology. 46:158-165 |
ISSN: | 1368-8375 |
Popis: | 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. |
Databáze: | OpenAIRE |
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