The ALDH1+ subpopulation of the human NMFH-1 cell line exhibits cancer stem-like characteristics

Abstract

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. Selfrenewal, 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).