Open AccessA Minority Subpopulation of CD 133 + / EGFR v III + / EGFR − Cells Acquires Stemness and Contributes to Gefitinib Resistance
Author(s) -
Liu XuJie,
Wu WenTao,
Wu WeiHua,
Yin Feng,
Ma SiHai,
Qin JiaZhen,
Liu XiuXiu,
Liu YiNan,
Zhang XiaoYan,
Li Peng,
Han Shuo,
Liu KaiYu,
Zhang JinMing,
He QiHua,
Shen Li
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12092
Subject(s) - gefitinib , epidermal growth factor receptor , neurosphere , cancer research , cell culture , cancer stem cell , chemistry , microbiology and biotechnology , stem cell , biology , in vitro , receptor , biochemistry , endothelial stem cell , adult stem cell , genetics
Summary Aims To study the contribution of epidermal growth factor receptor variant III ( EGFR v III ) to glioblastoma multiforme ( GBM ) stemness and gefitinib resistance. Methods CD 133 + and CD 133 − cells were separated from EGFR v III + clinical specimens of three patients with newly diagnosed GBM . Then, RT ‐ PCR was performed to evaluate EGFR v III and EGFR expression in CD 133 + and CD 133 − cells. The tumorigenicity and stemness of CD 133 + cells was verified by intracranial implantation of 5 × 10 3 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 CD 133 + cells expressed EGFR v III exclusively, while the CD 133 − cells expressed both EGFR v III and EGFR . At 6–8 weeks postimplantation, CD 133 + / EGFR v III + / EGFR − cells formed intracranial tumors. Cell counting kit‐8 results showed that the IC 50 values of the three isolated EGFR v III + cell lines treated with gefitinib were 14.44, 16.00, and 14.66 μM, respectively, whereas the IC 50 value of an isolated EGFR v III − cell line was 8.57 μM. Conclusions EGFR v III contributes to the stemness of cancer stem cells through coexpression with CD 133 in GBM s. Furthermore, CD 133 + / EGFR v III + / EGFR − cells have the ability to initiate tumor formation and may contribute to gefitinib resistance.