title: ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome.
abstract: Prostate cancer (PCa) contains a small population of cancer stem cells (CSCs) that contribute to its initiation and progression. The development of specific markers for identification of the CSCs may lead to new diagnostic strategies of PCa. Increased aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been found in the stem cell populations of leukemia and some solid tumors. The aim of the study was to investigate the stem-cell-related function and clinical significance of the ALDH1A1 in human PCa. ALDEFLUOR assay was used to isolate ALDH1A1(+) cells from PCa cell lines. Stem cell characteristics of the ALDH1A1(+) cells were then investigated by in vitro and in vivo approaches. The ALDH1A1 expression was also analyzed by immunohistochemistry in 18 normal prostate and 163 PCa tissues. The ALDH1A1(+) PCa cells showed high clonogenic and tumorigenic capacities, and serially reinitiated transplantable tumors that resembled histopathologic characteristics and heterogeneity of the parental PCa cells in mice. Immunohistochemical analysis of human prostate tissues showed that ALDH1A1(+) cells were sparse and limited to the basal component in normal prostates. However, in tumor specimens, increased ALDH1A1 immunopositivity was found not only in secretory type cancer epithelial cells but also in neuroendocrine tumor populations. Furthermore, the high ALDH1A1 expression in PCa was positively correlated with Gleason score (P=0.01) and pathologic stage (P=0.01), and inversely associated with overall survival and cancer-specific survival of the patients (P=0.00093 and 0.00017, respectively). ALDH1A1 could be a prostate CSC-related marker. Measuring its expression might provide a potential approach to study tumorigenesis of PCa and predict outcome of the disease.
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201-1192, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
authors.forename: Yuping
authors.initials: Y
authors.lastname: Mei
authors.forename: Qixin
authors.initials: Q
authors.lastname: Leng
authors.forename: Bingjie
authors.initials: B
authors.lastname: Leng
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Liu
authors.forename: Sanford A
authors.initials: SA
authors.lastname: Stass
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015197:Carcinogenicity Tests; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D050697:Retinal Dehydrogenase; D013234:Stem Cells; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase