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学科主题: 基础医学
题名:
A Minority Subpopulation of CD133+/EGFRvIII+/EGFR- Cells Acquires Stemness and Contributes to Gefitinib Resistance
作者: Liu, Xu-Jie1; Wu, Wen-Tao1; Wu, Wei-Hua1; Yin, Feng2; Ma, Si-Hai3; Qin, Jia-Zhen4; Liu, Xiu-Xiu1; Liu, Yi-Nan1; Zhang, Xiao-Yan1; Li, Peng1; Han, Shuo1; Liu, Kai-Yu5; Zhang, Jin-Ming6; He, Qi-Hua7; Shen, Li1
关键词: CD133 ; EGFRvIII ; Gefitinib resistance ; Stemness
刊名: CNS NEUROSCIENCE & THERAPEUTICS
发表日期: 2013-07-01
DOI: 10.1111/cns.12092
卷: 19, 期:7, 页:494-502
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences ; Pharmacology & Pharmacy
研究领域[WOS]: Neurosciences & Neurology ; Pharmacology & Pharmacy
关键词[WOS]: EPIDERMAL-GROWTH-FACTOR ; FACTOR RECEPTOR GENE ; CONFERS ENHANCED TUMORIGENICITY ; TYROSINE KINASE INHIBITOR ; TUMOR-INITIATING CELLS ; HUMAN-BRAIN TUMORS ; GLIOBLASTOMA-MULTIFORME ; ZD1839 IRESSA ; BREAST-CANCER ; HUMAN GLIOMAS
英文摘要:

Aims To study the contribution of epidermal growth factor receptor variant III (EGFRvIII) to glioblastoma multiforme (GBM) stemness and gefitinib resistance. Methods CD133+ and CD133- cells were separated from EGFRvIII+ clinical specimens of three patients with newly diagnosed GBM. Then, RT-PCR was performed to evaluate EGFRvIII and EGFR expression in CD133+ and CD133- cells. The tumorigenicity and stemness of CD133+ cells was verified by intracranial implantation of 5x103 cells into immunodeficient NOD/SCID mice. Finally, cells were evaluated for their sensitivity to EGFR tyrosine kinase inhibition by gefitinib. Results RT-PCR results showed that the sorted CD133+ cells expressed EGFRvIII exclusively, while the CD133- cells expressed both EGFRvIII and EGFR. At 6-8weeks postimplantation, CD133+/EGFRvIII+/EGFR- cells formed intracranial tumors. Cell counting kit-8 results showed that the IC50 values of the three isolated EGFRvIII+ cell lines treated with gefitinib were 14.44, 16.00, and 14.66M, respectively, whereas the IC50 value of an isolated EGFRvIII- cell line was 8.57M. Conclusions EGFRvIII contributes to the stemness of cancer stem cells through coexpression with CD133 in GBMs. Furthermore, CD133+/EGFRvIII+/EGFR- cells have the ability to initiate tumor formation and may contribute to gefitinib resistance.

语种: 英语
所属项目编号: 81272790
项目资助者: National Natural Science Foundation of China ; Foundation of National Science and Technology Major Project Focusing on Drug Innovation from The Ministry of Science and Technology of the People&prime ; s Republic of China
WOS记录号: WOS:000320197500004
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60227
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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作者单位: 1.PLA China, Navy Gen Hosp, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100871, Peoples R China
3.Beijing Union Med Coll Hosp, Beijing, Peoples R China
4.Beijing PLA, Mil Gen Hosp, Affiliated Bayi Brain Hosp, Beijing, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China
6.Peoples Liberat Army Gen Hosp, Dept Nucl Med, Beijing, Peoples R China
7.Peking Univ, Med & Hlth Anal Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Liu, Xu-Jie,Wu, Wen-Tao,Wu, Wei-Hua,et al. A Minority Subpopulation of CD133+/EGFRvIII+/EGFR- Cells Acquires Stemness and Contributes to Gefitinib Resistance[J]. CNS NEUROSCIENCE & THERAPEUTICS,2013,19(7):494-502.
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