ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome

Yu Chi Wang, Yi Te Yo, Hsin Yi Lee, Yu Ping Liao, Tai Kuang Chao, Po Hsuan Su, Hung Cheng Lai

Research output: Contribution to journalArticle

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Abstract

The role of aldehyde dehydrogenase 1 (ALDH1) as an ovarian cancer stem cell marker and its clinical significance have rarely been explored. We used an Aldefluor assay to isolate ALDH1-bright (ALDH1 br) cells from epithelial ovarian cancer cell lines and characterized the properties of the stem cells. ALDH1 br cells were enriched in ES-2 (1.3%), TOV-21G (1.0%), and CP70 (1.2%) cells. Both ALDH1 br and ALDH1 low cells repopulated stem cell heterogeneity, formed spheroids, and grew into tumors in immunocompromised mice, although these processes were more efficient in ALDH1 br cells. In the ES-2 and CP70 cells, ALDH1 br cells conferred more chemoresistance, and were more enriched in CD44 (by 1.74-fold and 5.18-fold, respectively) than in CD133 (by 1.39-fold and 1.17-fold, respectively), compared with ALDH1 low cells. Immunohistochemical staining for ALDH1 on a tissue microarray containing 84 epithelial ovarian cancer samples revealed that patients with higher ALDH1 expression (>50%) had poor overall survival, compared with those with lower ALDH1 (P = 0.004) and yielded an odds ratio of death of 2.43 (95% CI = 1.12 to 5.28) by multivariate analysis. The results did not support ALDH1 alone as an ovarian cancer stem cell marker, but demonstrated that ALDH1 is associated with CD44 expression, chemoresistance, and poor clinical outcome. The use of a combination of ALDH1 with other stem cell markers may help define ovarian cancer stem cells more stringently.

Original languageEnglish
Pages (from-to)1159-1169
Number of pages11
JournalAmerican Journal of Pathology
Volume180
Issue number3
DOIs
Publication statusPublished - Mar 2012
Externally publishedYes

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Drug Resistance
Neoplastic Stem Cells
Ovarian Neoplasms
Stem Cells
aldehyde dehydrogenase 1
Ovarian epithelial cancer
Multivariate Analysis
Biomarkers
Odds Ratio
Staining and Labeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. / Wang, Yu Chi; Yo, Yi Te; Lee, Hsin Yi; Liao, Yu Ping; Chao, Tai Kuang; Su, Po Hsuan; Lai, Hung Cheng.

In: American Journal of Pathology, Vol. 180, No. 3, 03.2012, p. 1159-1169.

Research output: Contribution to journalArticle

Wang, Yu Chi ; Yo, Yi Te ; Lee, Hsin Yi ; Liao, Yu Ping ; Chao, Tai Kuang ; Su, Po Hsuan ; Lai, Hung Cheng. / ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. In: American Journal of Pathology. 2012 ; Vol. 180, No. 3. pp. 1159-1169.
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abstract = "The role of aldehyde dehydrogenase 1 (ALDH1) as an ovarian cancer stem cell marker and its clinical significance have rarely been explored. We used an Aldefluor assay to isolate ALDH1-bright (ALDH1 br) cells from epithelial ovarian cancer cell lines and characterized the properties of the stem cells. ALDH1 br cells were enriched in ES-2 (1.3{\%}), TOV-21G (1.0{\%}), and CP70 (1.2{\%}) cells. Both ALDH1 br and ALDH1 low cells repopulated stem cell heterogeneity, formed spheroids, and grew into tumors in immunocompromised mice, although these processes were more efficient in ALDH1 br cells. In the ES-2 and CP70 cells, ALDH1 br cells conferred more chemoresistance, and were more enriched in CD44 (by 1.74-fold and 5.18-fold, respectively) than in CD133 (by 1.39-fold and 1.17-fold, respectively), compared with ALDH1 low cells. Immunohistochemical staining for ALDH1 on a tissue microarray containing 84 epithelial ovarian cancer samples revealed that patients with higher ALDH1 expression (>50{\%}) had poor overall survival, compared with those with lower ALDH1 (P = 0.004) and yielded an odds ratio of death of 2.43 (95{\%} CI = 1.12 to 5.28) by multivariate analysis. The results did not support ALDH1 alone as an ovarian cancer stem cell marker, but demonstrated that ALDH1 is associated with CD44 expression, chemoresistance, and poor clinical outcome. The use of a combination of ALDH1 with other stem cell markers may help define ovarian cancer stem cells more stringently.",
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