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BMC Cancer. 2012; 12: 329.
Published online Aug 1, 2012. doi:  10.1186/1471-2407-12-329
PMCID: PMC3458927
Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures
Yu-Ting Saw,1 Junzheng Yang,1 Shu-Kay Ng,2 Shubai Liu,1 Surendra Singh,3 Margit Singh,1 William R Welch,4 Hiroshi Tsuda,5 Wing-Ping Fong,6 David Thompson,3 Vasilis Vasiliou,3 Ross S Berkowitz,1 and Shu-Wing Ngcorresponding author1
1Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, 02115, USA
2School of Medicine, Griffith Health Institute, Griffith University, Meadowbrook, QLD, 4131, Australia
3Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, 80045, USA
4Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA
5Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, 160-8582, Japan
6School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China
corresponding authorCorresponding author.
Yu-Ting Saw: yutings/at/bu.edu; Junzheng Yang: junzhengy/at/gmail.com; Shu-Kay Ng: s.ng/at/griffith.edu.au; Shubai Liu: SLIU18/at/PARTNERS.ORG; Surendra Singh: SURENDRA.SINGH/at/UCDENVER.EDU; Margit Singh: singhmargit/at/gmail.com; William R Welch: WRWELCH/at/PARTNERS.ORG; Hiroshi Tsuda: htsud/at/s5.dion.ne.jp; Wing-Ping Fong: wpfong/at/cuhk.edu.hk; David Thompson: David.Thompson/at/ucdenver.edu; Vasilis Vasiliou: Vasilis.Vasiliou/at/ucdenver.edu; Ross S Berkowitz: Ross_Berkowitz/at/dfci.harvard.edu; Shu-Wing Ng: sng/at/rics.bwh.harvard.edu
Received April 9, 2012; Accepted July 18, 2012.
Abstract
Background
Aldehyde dehydrogenases belong to a superfamily of detoxifying enzymes that protect cells from carcinogenic aldehydes. Of the superfamily, ALDH1A1 has gained most attention because current studies have shown that its expression is associated with human cancer stem cells. However, ALDH1A1 is only one of the 19 human ALDH subfamilies currently known. The purpose of the present study was to determine if the expression and activities of other major ALDH isozymes are associated with human ovarian cancer and ovarian cancer sphere cultures.
Methods
Immunohistochemistry was used to delineate ALDH isozyme localization in clinical ovarian tissues. Western Blot analyses were performed on lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the immunohistochemistry findings. Quantitative reverse transcription-polymerase chain reactions were used to measure the mRNA expression levels. The Aldefluor® assay was used to measure ALDH activity in cancer cells from the four tumor subtypes.
Results
Immunohistochemical staining showed significant overexpression of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent, as seen from immunohistochemisty, Western blot analysis, and the Aldefluor® assay. The expression was elevated in the mucinous and endometrioid ovarian epithelial tumors than in serous and clear cell tumors. In some serous and most clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA expression of all studied ALDH isozymes also showed higher expression in endometrioid and mucinous tumors than in the serous and clear cell subtypes. The expression of ALDH enzymes showed tumor type-dependent induction in ovarian cancer cells growing as sphere suspensions in serum-free medium.
Conclusions
The results of our study indicate that ALDH enzyme expression and activity may be associated with specific cell types in ovarian tumor tissues and vary according to cell states. Elucidating the function of the ALDH isozymes in lineage differentiation and pathogenesis may have significant implications for ovarian cancer pathophysiology.
Keywords: Aldehyde dehydrogenase, Isozymes, Ovarian tumors, Sphere cultures, Tumor-type specific expression
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