ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome.

ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome.
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ALDH1A1 是恶性前列腺干细胞的标记物,也是前列腺癌患者预后的预测因子。

DOI:
10.1038/labinvest.2009.127
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发表时间:
2010-02
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
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中科院分区:
其他
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前列腺癌 (PCa) 含有少量癌症干细胞 (CSC),这些细胞有助于其发生和进展。开发用于识别 CSC 的特异性标记物可能会导致 PCa 的新诊断策略。在白血病和一些实体瘤的干细胞群中发现乙醛脱氢酶 1A1 (ALDH1A1) 活性增加。该研究的目的是探讨 ALDH1A1 在人类 PCa 中的干细胞相关功能和临床意义。 Aldeflor 测定用于从 PCa 细胞系中分离 ALDH1A1+ 细胞。然后通过体外和体内方法研究 ALDH1A1+ 细胞的干细胞特征。还通过免疫组织化学分析了 18 例正常前列腺和 163 例 PCa 组织中 ALDH1A1 的表达。 ALDH1A1+ PCa 细胞表现出高克隆形成和致瘤能力,并连续重新启动可移植肿瘤,类似于小鼠亲本 PCa 细胞的组织病理学特征和异质性。对人前列腺组织的免疫组织化学分析表明,正常前列腺中 ALDH1A1+ 细胞稀疏且仅限于基底成分。然而,在肿瘤标本中,不仅在分泌型癌症上皮细胞中发现了 ALDH1A1 免疫阳性增加,而且在神经内分泌肿瘤群体中也发现了这种增加。此外,PCa中ALDH1A1的高表达与Gleason评分(P=0.01)和病理分期(P=0.01)呈正相关,与患者的总生存期和癌症特异性生存期呈负相关(P=0.00093,P=0.00017)。 ALDH1A1 可能是前列腺 CSC 相关标记物。测量其表达可能为研究前列腺癌的肿瘤发生和预测疾病的结果提供一种潜在的方法。
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.
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