title: Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma.
abstract: Despite the introduction of 13-cis-retinoic acid (13-cis-RA) into the current chemotherapy, more than half of high-risk neuroblastoma patients have experienced tumor relapses driven by chemoresistant cancer stem cells (CSCs) that can be isolated by their ability to grow as spheres. Although aldehyde dehydrogenase (ALDH) has been used to characterize CSCs in certain cancers, ALDH remains elusive in neuroblastoma. In the present study, we determined ALDH activity and expression of its 19 isoforms in spheres and parental cells of neuroblastoma. ALDH activity and several ALDH isoforms were consistently induced in spheres of different neuroblastoma cells. While ALDH1A2, ALDH1L1 and ALDH3B2 expression was consistently induced in spheres and associated with the sphere and colony formation, only ALDH1A2 expression was significantly correlated with the poor prognosis of neuroblastoma patients. ALDH1A2 expression was further associated with the growth and undifferentiation of neuroblastoma xenografts and the resistance of neuroblastoma cells to 13-cis-RA. These results suggest that ALDH1A2 is involved in the regulation of CSC properties in neuroblastoma.
authors.affiliation: Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tri Budi
authors.initials: TB
authors.lastname: Hartomo
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Thi
authors.initials: T
authors.lastname: Van Huyen Pham
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirase
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Department of Medical Rehabilitation, Kobe Gakuin University, Kobe 651-2180, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hayakawa
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishimura
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D050697:Retinal Dehydrogenase / Q000037:antagonists & inhibitors / Q000502:physiology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase; D015474:Isotretinoin