2016 Fiscal Year Final Research Report
Identification of cancer stem-like cells of ovarian clear cell carcinoma and analysis of its chemotherapy-resistance mechanism
| Project/Area Number |
26462519
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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 |
Obstetrics and gynecology
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| Research Institution | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 卵巣癌 / 癌幹細胞 / 明細胞癌 |
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| Outline of Final Research Achievements |
We investigated the relationship between a CSC marker, aldehyde dehydrogenase1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. As a result, high ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. In vitro study revealed that ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system.
In conclusion, ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.
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| Free Research Field |
医歯薬学
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