Stem Cell Res Ther. 2013 Oct 25;4(5):132. doi: 10.1186/scrt343.
High expression of aldehyde dehydrogenase1A1 (ALDH1A1) is observed in many organs and tumors and may identify benign and cancer stem cell populations.
In the current study, the stem cell characteristics were determined in cells isolated from human prostate cell lines and clinical prostate specimens based upon the ALDEFLUOR™ assay. Cells isolated based on the ALDEFLUOR™ assay were compared to cells isolated based on ATP binding cassette transporter G2 (ABCG2) activity using the side population assay. To test for stem cell characteristics of self-renewal and multipotency, cells with high and low ALDH1A1 activity, based on the ALDEFLUOR™ assay (ALDHHi and ALDH Low), were isolated from prostate clinical specimens and were recombined with rat urogenital sinus mesenchyme to induce prostate gland formation.
The percentage of ALDH Hi cells in prostate cell lines (RWPE-1, RWPE-2, CWR-R1, and DU-145) was 0.5 to 6%, similarly in non-tumor and tumor clinical specimens the percentage of ALDH Hi cells was 0.6 to 4%. Recombinants using ALDH Hi cells serially generated prostate tissue up to three generations with as few as 250 starting cells. Immunohistochemical analysis of the recombinants using ALDHHi cells contained prostatic glands frequently expressing androgen receptor (AR), p63, chromogranin A, ALDH1A1, ABCG2, and prostate specific antigen (PSA), compared to their ALDH Low counterparts. Inhibition of ALDH resulted in the reduction of sphere formation capabilities in the CWR-R1, but not in the RWPE-2 and DU-145, prostate cell lines. ABCG2 inhibition resulted in a more robust decrease of sphere formation in androgen sensitive cell lines, CWR-R1 and RWPE-2, but not androgen insensitive DU-145. ALDH1A1 expression was enriched in ALDH Hi cells and non-side population cells. ABCG2 expression was only enriched in side population cells.
The percentage of ALDHHi cells in prostate cell lines and prostate tissue was consistently higher compared to cells with high ABCG2 activity, identified with the side population assay. The expression of the stem and differentiation markers indicates the ALDH Hi recombinants contained cells with self-renewal and multipotency activity. When the two assays were directly compared, cells with the side population phenotype demonstrated more stem cell potential in the tissue recombination assay compared to ALDH Hi cells. The increased stem cell potential of side population cells in the tissue recombination assay and the decrease in sphere formation when ABCG2 is inhibited indicates that the side population enriches for prostate stem cells.
醛脱氢酶 1A1（ALDH1A1）在许多器官和肿瘤中表达水平较高，可能可以识别良性和癌症干细胞群体。
在目前的研究中，根据 ALDEFLUOR™分析，从人前列腺细胞系和临床前列腺标本中分离的细胞确定了干细胞特征。基于 ALDEFLUOR™分析分离的细胞与使用侧群分析基于三磷酸腺苷结合盒转运蛋白 G2（ABCG2）活性分离的细胞进行了比较。为了测试自我更新和多能性的干细胞特性，根据 ALDEFLUOR™分析（ALDHHi 和 ALDH Low）从前列腺临床标本中分离出高和低 ALDH1A1 活性的细胞，并与大鼠泌尿生殖窦基质重组，以诱导前列腺形成。
前列腺细胞系（RWPE-1、RWPE-2、CWR-R1 和 DU-145）中 ALDH Hi 细胞的百分比为 0.5%至 6%，非肿瘤和肿瘤临床标本中 ALDH Hi 细胞的百分比也为 0.6%至 4%。使用 ALDH Hi 细胞的重组体使用多达 250 个起始细胞可连续产生三代前列腺组织。使用 ALDHHi 细胞的重组体的免疫组织化学分析包含经常表达雄激素受体（AR）、p63、嗜铬粒蛋白 A、ALDH1A1、ABCG2 和前列腺特异性抗原（PSA）的前列腺腺，与它们的 ALDH Low 对应物相比。在 CWR-R1 中，ALDH 的抑制导致球体形成能力降低，但在 RWPE-2 和 DU-145 前列腺细胞系中则没有。ABCG2 抑制导致对雄激素敏感的细胞系（CWR-R1 和 RWPE-2）中球体形成的减少更为明显，但对雄激素不敏感的 DU-145 则没有。ALDH1A1 表达在 ALDH Hi 细胞和非侧群细胞中富集。ABCG2 表达仅在侧群细胞中富集。
与使用侧群分析鉴定的具有高 ABCG2 活性的细胞相比，前列腺细胞系和前列腺组织中 ALDHHi 细胞的百分比始终更高。干细胞和分化标志物的表达表明，ALDH Hi 重组体包含具有自我更新和多能性活性的细胞。当直接比较这两种检测方法时，与 ALDH Hi 细胞相比，具有侧群表型的细胞在组织重组检测中显示出更高的干细胞潜力。在组织重组检测中侧群细胞的干细胞潜力增加以及 ABCG2 抑制时球体形成减少表明侧群细胞富集了前列腺干细胞。
Zotero 插件
