Nakahata Kengo, Uehara Shuichiro, Nishikawa Shimpei, Kawatsu Miyoko, Zenitani Masahiro, Oue Takaharu, Okuyama Hiroomi
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
PLoS One. 2015 Apr 27;10(4):e0125454. doi: 10.1371/journal.pone.0125454. eCollection 2015.
Cancer stem cells (CSCs) are defined as a small population of cancer cells with the properties of high self-renewal, differentiation, and tumor-initiating functions. Recent studies have demonstrated that aldehyde dehydrogenase 1 (ALDH1) is a marker for CSCs in adult cancers. Although CSCs have been identified in some different types of pediatric solid tumors, there have been no studies regarding the efficacy of ALDH1 as a marker for CSCs. Therefore, in order to elucidate whether ALDH1 can be used as a marker for CSCs of pediatric sarcoma, we examined the characteristics of a population of cells with a high ALDH1 activity (ALDH1high cells) in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. We used the human embryonal RMS (eRMS) cell lines RD and KYM-1, and sorted the cells into two subpopulations of ALDH1high cells and cells with a low ALDH1 activity (ALDH1low cells). Consequently, we found that the ALDH1high cells comprised 3.9% and 8.2% of the total cell population, respectively, and showed a higher capacity for self-renewal and tumor formation than the ALDH1low cells. With regard to chemoresistance, the survival rate of the ALDH1high cells was found to be higher than that of the ALDH1low cells following treatment with chemotherapeutic agents for RMS. Furthermore, the ALDH1high cells exhibited a higher degree of pluripotency and gene expression of Sox2, which is one of the stem cell markers. Taken together, the ALDH1high cells possessed characteristics of CSCs, including colony formation, chemoresistance, differentiation and tumor initiation abilities. These results suggest that ALDH1 is a potentially useful marker of CSCs in eRMS.
癌症干细胞（CSCs）被定义为一小群具有高度自我更新、分化和肿瘤起始功能的癌细胞。最近的研究表明，醛脱氢酶1（ALDH1）是成人癌症中CSCs的一个标志物。尽管在一些不同类型的儿童实体瘤中已鉴定出CSCs，但关于ALDH1作为CSCs标志物的有效性尚无研究。因此，为了阐明ALDH1是否可作为儿童肉瘤CSCs的标志物，我们检测了横纹肌肉瘤（RMS，儿童最常见的软组织肉瘤）中具有高ALDH1活性的细胞群体（ALDH1高细胞）的特征。我们使用了人胚胎性RMS（eRMS）细胞系RD和KYM-1，并将细胞分选成ALDH1高细胞和ALDH1活性低的细胞（ALDH1低细胞）两个亚群。结果，我们发现ALDH1高细胞分别占总细胞群体的3.9%和8.2%，并且显示出比ALDH1低细胞更高的自我更新和肿瘤形成能力。关于化疗耐药性，在用RMS化疗药物处理后，发现ALDH1高细胞的存活率高于ALDH1低细胞。此外，ALDH1高细胞表现出更高程度的多能性以及干细胞标志物之一Sox2的基因表达。综上所述，ALDH1高细胞具有CSCs的特征，包括集落形成、化疗耐药性、分化和肿瘤起始能力。这些结果表明，ALDH1是eRMS中CSCs的一个潜在有用的标志物。
