TY - JOUR
T1 - ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients outcome
AU - Li, Ting
AU - Su, Yun
AU - Mei, Yuping
AU - Leng, Qixin
AU - Leng, Bingjie
AU - Liu, Zhenqiu
AU - Stass, Sanford A.
AU - Jiang, Feng
N1 - Funding Information:
This work was supported in part by the National Cancer Institute Grants CA-113707 and CA-133956; American Cancer Society-Research Scholar Grant in Basic, Preclinical, Clinical and Epidemiology Research; a Scholar Award from NIH-K12-Multidisciplinary Clinical Research Career Development Program-University of Maryland; and a clinical innovator award from Flight Attendant Medical Research Institute (all to FJ).
PY - 2010/2
Y1 - 2010/2
N2 - 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 (P0.01) and pathologic stage (P0.01), and inversely associated with overall survival and cancer-specific survival of the patients (P0.00093 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.
AB - 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 (P0.01) and pathologic stage (P0.01), and inversely associated with overall survival and cancer-specific survival of the patients (P0.00093 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.
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U2 - 10.1038/labinvest.2009.127
DO - 10.1038/labinvest.2009.127
M3 - Article
C2 - 20010854
AN - SCOPUS:75949101677
SN - 0023-6837
VL - 90
SP - 234
EP - 244
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 2
ER -