2015 Fiscal Year Final Research Report
Role of hypoxia and cancer stem cells in the resistance to EGFR-TKI in non-small cell lung cancer
| Project/Area Number |
24591176
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Fumiyuki 順天堂大学, 医学部, 准教授 (70327823)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Keywords | 非小細胞肺癌 / 癌幹細胞 / EGFR-TKI 耐性 |
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| Outline of Final Research Achievements |
Our aim here was to elucidate the role of hypoxia and cancer stem cells (CSCs) in the resistance to EGFR-TKI in non-small cell lung cancer (NSCLC). PC9 and HCC827 were exposed to high concentration of gefitinib under normoxic or hypoxic conditions. Seven days after gefitinib exposure, a small fraction of viable cells were detected, and these were referred to as “gefitinib-resistant persisters” (GRPs). Stem cell genes, such as CD133 and Oct4, were highly expressed, and GRPs exhibited a high potential for tumorigenicity in vivo and self-renewal capability. Importantly, hypoxic exposure significantly increased phosphorylation of IGF1R, and the population of CD133- and Oct4-positive GRPs. Transfection of Oct4 significantly increased CD133-positive GRPs and sphere formation under the treatment of gefitinib. Interestingly, gefitinib resistance induced by high Oct4 expression was more evident under the hypoxia.
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| Free Research Field |
肺癌
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