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A minority subpopulation of CD133(+) /EGFRvIII(+) /EGFR(-) cells acquires stemness and contributes to gefitinib resistance.


ABSTRACT:

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 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 CD133(+) cells expressed EGFRvIII exclusively, while the CD133(-) cells expressed both EGFRvIII and EGFR. At 6-8 weeks 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 14.66 ?M, respectively, whereas the IC50 value of an isolated EGFRvIII(-) cell line was 8.57 ?M.

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.

SUBMITTER: Liu XJ 

PROVIDER: S-EPMC6493376 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

A minority subpopulation of CD133(+) /EGFRvIII(+) /EGFR(-) cells acquires stemness and contributes to gefitinib resistance.

Liu Xu-Jie XJ   Wu Wen-Tao WT   Wu Wei-Hua WH   Yin Feng F   Ma Si-Hai SH   Qin Jia-Zhen JZ   Liu Xiu-Xiu XX   Liu Yi-Nan YN   Zhang Xiao-Yan XY   Li Peng P   Han Shuo S   Liu Kai-Yu KY   Zhang Jin-Ming JM   He Qi-Hua QH   Shen Li L  

CNS neuroscience & therapeutics 20130410 7


<h4>Aims</h4>To study the contribution of epidermal growth factor receptor variant III (EGFRvIII) to glioblastoma multiforme (GBM) stemness and gefitinib resistance.<h4>Methods</h4>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 5  ...[more]

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