Aldehyde Dehydrogenase 1 (ALDH1) Is a Potential Marker for Cancer Stem Cells in Embryonal Rhabdomyosarcoma.
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.
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Kengo
K
Nakahata
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Shuichiro
S
Uehara
Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
Shimpei
S
Nishikawa
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Miyoko
M
Kawatsu
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Masahiro
M
Zenitani
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Takaharu
T
Oue
Departments of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Hiroomi
H
Okuyama
D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D019008:Drug Resistance, Neoplasm; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D016688:Mice, Inbred NOD; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology*; D060888:Real-Time Polymerase Chain Reaction; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy / Q000201:enzymology*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase