A Minority Subpopulation of CD133+/EGFRvIII+/EGFR− Cells Acquires Stemness and Contributes to Gefitinib Resistance. (10th April 2013)

• Record Type: Journal Article
• Authors: Liu, Xu‐Jie; Wu, Wen‐Tao; Wu, Wei‐Hua; Yin, Feng; Ma, Si‐Hai; Qin, Jia‐Zhen; Liu, Xiu‐Xiu; Liu, Yi‐Nan; Zhang, Xiao‐Yan; Li, Peng; Han, Shuo; Liu, Kai‐Yu; Zhang, Jin‐Ming; He, Qi‐Hua; Shen, Li
• Is Part Of: CNS neuroscience & therapeutics. Volume 19:Number 7(2013)
• Page Start: 494
• Page End: 502
• Publication Date: 2013-04-10
• Subjects: Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12092
• Languages: English
• ISSNs: 1755-5930

Abstract

<abstract abstract-type="main" id="cns12092-abs-0001"> <title>Summary</title> <sec id="cns12092-sec-0001" sec-type="section"> <title>Aims</title> <p>To study the contribution of epidermal growth factor receptor variant III (EGFRvIII) to glioblastoma multiforme (GBM) stemness and gefitinib resistance.</p> </sec> <sec id="cns12092-sec-0002" sec-type="section"> <title>Methods</title> <p>CD133<sup>+</sup> and CD133<sup>−</sup> cells were separated from EGFRvIII<sup>+</sup> clinical specimens of three patients with newly diagnosed GBM. Then, RT‐PCR was performed to evaluate EGFRvIII and EGFR expression in CD133<sup>+</sup> and CD133<sup>−</sup> cells. The tumorigenicity and stemness of CD133<sup>+</sup> cells was verified by intracranial implantation of 5 × 10<sup>3</sup> cells into immunodeficient NOD/SCID mice. Finally, cells were evaluated for their sensitivity to EGFR tyrosine kinase inhibition by gefitinib.</p> </sec> <sec id="cns12092-sec-0003" sec-type="section"> <title>Results</title> <p>RT‐PCR results showed that the sorted CD133<sup>+</sup> cells expressed EGFRvIII exclusively, while the CD133<sup>−</sup> cells expressed both EGFRvIII and EGFR. At 6–8 weeks postimplantation, CD133<sup>+</sup>/EGFRvIII<sup>+</sup>/EGFR<sup>−</sup> cells formed intracranial tumors. Cell counting kit‐8 results showed that the IC<sub>50</sub> values of the three isolated EGFRvIII<sup>+</sup> cell lines treated with gefitinib were 14.44, 16.00, and 14.66 μM, respectively, whereas the IC<sub>50</sub> value of an isolated EGFRvIII<sup>−</sup> cell line was 8.57 μM.</p> </sec> <sec id="cns12092-sec-0004" sec-type="section"> <title>Conclusions</title> <p>EGFRvIII contributes to the stemness of cancer stem cells through coexpression with CD133 in GBMs. Furthermore, CD133<sup>+</sup>/EGFRvIII<sup>+</sup>/EGFR<sup>−</sup> cells have the ability to initiate tumor formation and may contribute to gefitinib resistance.</p> </sec> </abstract>