title: 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. 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).
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Tong
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal; D002945:Cisplatin; D004317:Doxorubicin; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D051677:Histiocytoma, Malignant Fibrous / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004317:Doxorubicin; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; D063150:Polycomb Repressive Complex 1; D002945:Cisplatin