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A Minority Subpopulation of CD 133 + / EGFR v III + / EGFR ? Cells Acquires Stemness and Contributes to Gefitinib Resistance

机译:CD 133 + / EGFR v III + / EGFR的少数族群?细胞获得干性并促进吉非替尼耐药

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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 × 103 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.
机译:概述目的研究表皮生长因子受体变体III(EGFR v III)对多形性胶质母细胞瘤(GBM)茎和吉非替尼耐药性的影响。方法CD 133+和CD 133?从3例新诊断的GBM患者的EGFR v III +临床标本中分离细胞。然后,进行RT‐PCR评估CD 133+和CD 133?中的EGFR v III和EGFR表达。细胞。通过将5×103细胞颅内植入免疫缺陷的NOD / SCID小鼠中,验证了CD 133+细胞的致瘤性和干性。最后,评估了吉非替尼对细胞对EGFR酪氨酸激酶抑制的敏感性。结果RT ‐ PCR结果显示,分选的CD 133+细胞仅表达EGFR v III,而CD 133?细胞表达EGFR v III和EGFR。植入后6-8周,CD 133 + / EGFR v III + / EGFR?细胞形成颅内肿瘤。细胞计数试剂盒8结果表明,用吉非替尼处理的三种分离的EGFR v III +细胞系的IC 50值分别为14.44、16.00和14.66μM,而分离的EGFR v III +细胞的IC 50值则为50。细胞系为8.57μM。结论EGFR v III通过与CD 133在GBM中共表达而有助于癌症干细胞的干性。此外,CD 133 + / EGFR v III + / EGFR?细胞具有启动肿瘤形成的能力,并可能有助于吉非替尼耐药。

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