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Deng S , Yang XJ , Lassus H , Liang S , Kaur S , Ye QR , Li CS , Wang LP , Roby KF , Orsulic S , Connolly DC , Zhang YC , Montone K , Butzow R , Coukos G , Zhang L
Distinct Expression Levels and Patterns of Stem Cell Marker, Aldehyde Dehydrogenase Isoform 1 (ALDH1), in Human Epithelial Cancers
Plos One. 2010 Apr;5(4) :E10277
PMID: ISI:000276952500022    PMCID: PMCID: PMC2858084   
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Abstract
Aldehyde dehydrogenase isoform 1 (ALDH1) has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036). Finally, ALDH(br) tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.
Notes
Deng, Shan Yang, Xiaojun Lassus, Heini Liang, Shun Kaur, Sippy Ye, Qunrui Li, Chunsheng Wang, Li-Ping Roby, Katherine F. Orsulic, Sandra Connolly, Denise C. Zhang, Youcheng Montone, Kathleen Butzow, Ralf Coukos, George Zhang, Lin Breast Cancer Alliance ; Ovarian Cancer Research Found ; Mary Kay Ash Charitable Foundation ; National Cancer Institute [R01CA142776, P50-CA83638-7951]; US Department of Defense [W81XWH-10-1-0082] This work was supported by grants from the Breast Cancer Alliance (LZ), the Ovarian Cancer Research Found (Liz Tilberis Scholar, LZ), the Mary Kay Ash Charitable Foundation (LZ), National Cancer Institute (R01CA142776 and Ovarian Cancer SPORE P50-CA83638-7951 project 3, LZ), and US Department of Defense (W81XWH-10-1-0082, LZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 53 Public library science; 185 berry st, ste 1300, san francisco, ca 94107 usa 586ys