Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers

• Published in: PloS one 2010-04, Vol.5 (4), p.e10277-e10277
• Main Authors: 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, Bützow, Ralf, Coukos, George, Zhang, Lin
• Format: Article
• Language: English
• Subjects: Aldehyde dehydrogenase; Aldehydes; Analysis; Animals; Biomarkers - analysis; Biotechnology; Bone cancer; Breast cancer; Cancer; Cancer research; Carcinoma - diagnosis; Carcinoma - enzymology; Cell culture; Cell Line, Tumor; Chemotherapy; Colon; Colon cancer; Correlation analysis; Dehydrogenase; Dehydrogenases; Enzymatic activity; Epithelial Cells - enzymology; Female; Gene Expression; Genetic engineering; Gynecology; Humans; Immunohistochemistry; Inflammatory bowel disease; Isoenzymes - analysis; Laboratories; Lung cancer; Medical research; Metastasis; Mice; Mice, Transgenic; Neoplastic Stem Cells - enzymology; Obstetrics; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - pathology; Pathology; Pathology/Molecular Pathology; Prognosis; Retinal Dehydrogenase - analysis; Rodents; Stem cell research; Stem cell transplantation; Stem cells; Tissues; Transgenic mice; Tumor cell lines; Tumor cells; Tumorigenesis; Tumors; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010277

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.