Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Am J Pathol. 2012 Mar;180(3):1159-1169. doi: 10.1016/j.ajpath.2011.11.015. Epub 2012 Jan 2.
The role of aldehyde dehydrogenase 1 (ALDH1) as an ovarian cancer stem cell marker and its clinical significance have rarely been explored. We used an Aldefluor assay to isolate ALDH1-bright (ALDH1(br)) cells from epithelial ovarian cancer cell lines and characterized the properties of the stem cells. ALDH1(br) cells were enriched in ES-2 (1.3%), TOV-21G (1.0%), and CP70 (1.2%) cells. Both ALDH1(br) and ALDH1(low) cells repopulated stem cell heterogeneity, formed spheroids, and grew into tumors in immunocompromised mice, although these processes were more efficient in ALDH1(br) cells. In the ES-2 and CP70 cells, ALDH1(br) cells conferred more chemoresistance, and were more enriched in CD44 (by 1.74-fold and 5.18-fold, respectively) than in CD133 (by 1.39-fold and 1.17-fold, respectively), compared with ALDH1(low) cells. Immunohistochemical staining for ALDH1 on a tissue microarray containing 84 epithelial ovarian cancer samples revealed that patients with higher ALDH1 expression (>50%) had poor overall survival, compared with those with lower ALDH1 (P = 0.004) and yielded an odds ratio of death of 2.43 (95% CI = 1.12 to 5.28) by multivariate analysis. The results did not support ALDH1 alone as an ovarian cancer stem cell marker, but demonstrated that ALDH1 is associated with CD44 expression, chemoresistance, and poor clinical outcome. The use of a combination of ALDH1 with other stem cell markers may help define ovarian cancer stem cells more stringently.
醛脱氢酶 1（ALDH1）作为卵巢癌干细胞标志物的作用及其临床意义很少被探讨。我们使用 Aldefluor 测定法从上皮性卵巢癌细胞系中分离出 ALDH1 阳性（ALDH1(br)）细胞，并对这些干细胞的特性进行了表征。ALDH1(br)细胞在上皮性卵巢癌细胞系 ES-2（1.3%）、TOV-21G（1.0%）和 CP70（1.2%）中富集。ALDH1(br)和 ALDH1(low)细胞均能重新生成干细胞异质性，形成球体，并在免疫缺陷小鼠中长成肿瘤，尽管在 ALDH1(br)细胞中这些过程更为有效。在 ES-2 和 CP70 细胞中，ALDH1(br)细胞赋予了更高的化疗耐药性，与 ALDH1(low)细胞相比，CD44 的表达更丰富（分别增加 1.74 倍和 5.18 倍），而 CD133 的表达更丰富（分别增加 1.39 倍和 1.17 倍）。在包含 84 例上皮性卵巢癌样本的组织微阵列上进行的 ALDH1 免疫组织化学染色显示，与 ALDH1 表达较低的患者相比（P=0.004），ALDH1 表达较高（>50%）的患者总体生存较差，多变量分析得出死亡的比值比为 2.43（95%CI=1.12 至 5.28）。结果不支持 ALDH1 单独作为卵巢癌干细胞标志物，但表明 ALDH1 与 CD44 表达、化疗耐药性和不良临床结局相关。联合使用 ALDH1 与其他干细胞标志物可能有助于更严格地定义卵巢癌干细胞。
