Abstract | OBJECTIVE: METHODS: Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. RESULTS: High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. 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. CONCLUSIONS: 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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Authors | T Mizuno, N Suzuki, H Makino, T Furui, E Morii, H Aoki, T Kunisada, M Yano, S Kuji, Y Hirashima, A Arakawa, S Nishio, K Ushijima, K Ito, Y Itani, K Morishige |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 137
Issue 2
Pg. 299-305
(May 2015)
ISSN: 1095-6859 [Electronic] United States |
PMID | 25541259
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Isoenzymes
- Reactive Oxygen Species
- Aldehyde Dehydrogenase 1 Family
- ALDH1A1 protein, human
- Retinal Dehydrogenase
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Topics |
- Adenocarcinoma, Clear Cell
(metabolism, pathology)
- Adult
- Aged
- Aged, 80 and over
- Aldehyde Dehydrogenase 1 Family
- Carcinoma, Ovarian Epithelial
- Cell Line, Tumor
- Female
- Humans
- Immunohistochemistry
- Isoenzymes
(metabolism)
- Middle Aged
- Neoplasms, Glandular and Epithelial
(metabolism, pathology)
- Neoplastic Stem Cells
(enzymology, metabolism, pathology)
- Ovarian Neoplasms
(metabolism, pathology)
- Prognosis
- Reactive Oxygen Species
(metabolism)
- Retinal Dehydrogenase
(metabolism)
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