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

Oncol Rep. 2015 May;33(5):2291-8. doi: 10.3892/or.2015.3842. Epub 2015 Mar 9.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • Aldehyde Dehydrogenase 1 Family
  • Animals
  • Antineoplastic Agents
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Self Renewal
  • Cisplatin
  • Doxorubicin
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc
  • Histiocytoma, Malignant Fibrous / enzymology*
  • Histiocytoma, Malignant Fibrous / genetics
  • Humans
  • Isoenzymes / metabolism*
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / genetics
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / metabolism*
  • Polycomb Repressive Complex 1 / genetics
  • RNA, Messenger / metabolism*
  • Retinal Dehydrogenase / metabolism*
  • STAT3 Transcription Factor / genetics

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • BMI1 protein, human
  • Biomarkers, Tumor
  • Isoenzymes
  • Neoplasm Proteins
  • RNA, Messenger
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Doxorubicin
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase
  • Polycomb Repressive Complex 1
  • Cisplatin