ALDH1A1 Is a Marker for Malignant Prostate Stem Cells and Predictor of Prostate Cancer Patients’ Outcome

Prostate cancer (PCa) contains small population of cancer stem cells (CSCs) that contribute to its initiation and progression. 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 stem cell populations of leukemia and some solid tumors. The goal 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. ALDH1A1 expression by immunohistochemestry in 18 normal prostate and 163 PCa tissues was also analyzed. The ALDH1A1(+) PCa cells displayed 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. In tumor specimens, however, 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, P=0.00017). 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.