Abstract
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma, Clear Cell / diagnosis
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Adenocarcinoma, Clear Cell / enzymology
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Adenocarcinoma, Clear Cell / genetics*
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Adenocarcinoma, Clear Cell / pathology
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Adult
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Aged
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Aldehyde Dehydrogenase 1 Family
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Cell Line, Tumor
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Cystadenocarcinoma, Serous / diagnosis
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Cystadenocarcinoma, Serous / enzymology
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Cystadenocarcinoma, Serous / genetics*
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Cystadenocarcinoma, Serous / pathology
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Female
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Gene Expression*
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Humans
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Isoenzymes / genetics*
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Isoenzymes / metabolism
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Middle Aged
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Neoplasm Staging
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Organ Specificity
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Ovarian Neoplasms / diagnosis
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Ovarian Neoplasms / enzymology
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Ovarian Neoplasms / genetics*
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Ovarian Neoplasms / pathology
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Primary Cell Culture
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Prognosis
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Retinal Dehydrogenase / genetics*
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Retinal Dehydrogenase / metabolism
Substances
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Biomarkers, Tumor
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Isoenzymes
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Aldehyde Dehydrogenase 1 Family
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ALDH1A1 protein, human
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Retinal Dehydrogenase
Grants and funding
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant numbers 16209013, 17016061 and 15659097) for Practical Application Research from the Japan Science and Technology Agency, and for Cancer Research (15–17 and 19–14) from the Ministry of Health, Labor and Welfare of Japan, Ono Cancer Research Fund (to NS) and Takeda Science Foundation (to YH). This work was supported in part by the National Cancer Center Research and Development Fund (23-A-44). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.