Li Dejian, Zhang Tao, Gu Wenguang, Li Peng, Cheng Xiangyang, Tong Tiejun, Wang Wenbo
Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Oncol Rep. 2015 May;33(5):2291-8. doi: 10.3892/or.2015.3842. Epub 2015 Mar 9.
Cancer stem cells (CSCs) have been reported in many tissues. However, CSCs have yet to be identified in a human malignant fibrous histiocytoma (MFH) cell line. Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as a stem cell marker for isolating CSCs from cancer. The aim of the present study was to identify a population with elevated ALDH in the human NMFH-1 cell line. ALDH⁺ and ALDH- cell populations were isolated and compared for CSC characteristics. ALDH enzymatic activity was used as a marker to identify the cells in the NMFH-1 line. Self-renewal, differentiation capacity, and tumorigenicity of the NMFH-1 ALDH⁺ cell population were then examined using a spheroid formation assay and xenograft model in nude mice. Chemoresistance levels, ABCG2 drug transport gene expression, and stem cell-associated gene expression were compared in these NMFH-1 populations. The ALDH⁺ population was better able to form spheres in anchorage-independent serum-starved conditions. Furthermore, the mRNA expression of key stem cell-related genes was enhanced in these cells. Increased expression of the drug transporter gene, ABCG2, was detected. Compared with ALDH-, the ALDH⁺ subpopulation had higher levels of chemoresistance to doxorubicin (DXR) and cisplatin (CDDP). Additionally, the ALDH⁺ cells more efficiently formed tumors when implanted into BALB/c nude mice. ALDH1 may therefore be used as a marker for the isolation of cells that exhibit several characteristics of CSCs from the NMFH-1 cell line. This finding may lead to the development of novel therapies to specifically kill ALDH1⁺ subpopulations (CSCs).
癌症干细胞（CSCs）已在许多组织中被报道。然而，人类恶性纤维组织细胞瘤（MFH）细胞系中尚未鉴定出CSCs。醛脱氢酶1（ALDH1）水平升高被认为是从癌症中分离CSCs的干细胞标志物。本研究的目的是在人类NMFH-1细胞系中鉴定出ALDH水平升高的细胞群体。分离出ALDH⁺和ALDH⁻细胞群体，并比较它们的CSC特征。使用ALDH酶活性作为标志物来鉴定NMFH-1细胞系中的细胞。然后，通过球体形成试验和裸鼠异种移植模型检测NMFH-1 ALDH⁺细胞群体的自我更新、分化能力和致瘤性。比较这些NMFH-1细胞群体中的化疗耐药水平、ABCG2药物转运基因表达和干细胞相关基因表达。ALDH⁺群体在无锚定血清饥饿条件下更能形成球体。此外，这些细胞中关键干细胞相关基因的mRNA表达增强。检测到药物转运基因ABCG2的表达增加。与ALDH⁻相比，ALDH⁺亚群对阿霉素（DXR）和顺铂（CDDP）具有更高的化疗耐药水平。此外，将ALDH⁺细胞植入BALB/c裸鼠时，能更有效地形成肿瘤。因此，ALDH1可用作从NMFH-1细胞系中分离出具有CSCs若干特征细胞的标志物。这一发现可能会促成开发出特异性杀死ALDH1⁺亚群（CSCs）的新疗法。
