Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma

Hartomo,Tri Budi; Van Huyen Pham,Thi; Yamamoto,Nobuyuki; Hirase,Satoshi; Hasegawa,Daiichiro; Kosaka,Yoshiyuki; Matsuo,Masafumi; Hayakawa,Akira; Takeshima,Yasuhiro; Iijima,Kazumoto; Nishio,Hisahide; Nishimura,Noriyuki

doi:10.3892/ijo.2014.2801

Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma

Authors:
- Tri Budi Hartomo
- Thi Van Huyen Pham
- Nobuyuki Yamamoto
- Satoshi Hirase
- Daiichiro Hasegawa
- Yoshiyuki Kosaka
- Masafumi Matsuo
- Akira Hayakawa
- Yasuhiro Takeshima
- Kazumoto Iijima
- Hisahide Nishio
- Noriyuki Nishimura
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Affiliations: Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan, Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan, Department of Medical Rehabilitation, Kobe Gakuin University, Kobe 651-2180, Japan
Published online on: December 17, 2014 https://doi.org/10.3892/ijo.2014.2801
Pages: 1089-1098

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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.

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