Burger Patricia E, Gupta Rashmi, Xiong Xiaozhong, Ontiveros Christopher S, Salm Sarah N, Moscatelli David, Wilson E Lynette
Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Stem Cells. 2009 Sep;27(9):2220-8. doi: 10.1002/stem.135.
We have shown previously that prostatic stem/progenitor cells can be purified from isolated prostate ducts, based on their high expression of the Sca-1 surface antigen. We now report that high levels of aldehyde dehydrogenase (ALDH) activity are present in a subset of prostate epithelial cells that coexpress a number of antigens found on stem/progenitor cells of other origins (CD9, Bcl-2, CD200, CD24, prominin, Oct 3/4, ABCG2, and nestin). Almost all of these cells expressing high levels of ALDH activity also express Sca-1 and a third of them express high levels of this antigen. The cells with high levels of ALDH activity have greater in vitro proliferative potential than cells with low ALDH activity. Importantly, in an in vivo prostate reconstitution assay, the cells expressing high levels of ALDH activity were much more effective in generating prostatic tissue than a population of cells with low enzymatic activity. Thus, a high level of ALDH activity can be considered a functional marker of prostate stem/progenitor cells and allows for simple, efficient isolation of cells with primitive features. The elucidation of the role of ALDH in prostate stem/progenitor cells may lead to the development of rational therapies for treating prostate cancer and benign prostatic hyperplasia.
我们之前已经表明,基于其Sca-1表面抗原的高表达,前列腺干/祖细胞可以从分离的前列腺导管中纯化出来。我们现在报告,醛脱氢酶(ALDH)活性的高水平存在于一部分前列腺上皮细胞中,这些细胞共表达在其他来源的干/祖细胞上发现的多种抗原(CD9、Bcl-2、CD200、CD24、prominin、Oct 3/4、ABCG2和巢蛋白)。几乎所有这些表达高水平ALDH活性的细胞也表达Sca-1,其中三分之一表达该抗原的高水平。具有高水平ALDH活性的细胞比具有低ALDH活性的细胞具有更大的体外增殖潜力。重要的是,在体内前列腺重建试验中,表达高水平ALDH活性的细胞在生成前列腺组织方面比具有低酶活性的细胞群体更有效。因此,高水平的ALDH活性可以被认为是前列腺干/祖细胞的功能标志物,并允许简单、有效地分离具有原始特征的细胞。对ALDH在前列腺干/祖细胞中的作用的阐明可能会导致开发治疗前列腺癌和良性前列腺增生的合理疗法。