The role of aldehyde dehydrogenase 1A1 in stem cells and cancer stem cells

H. Tomita, Kaori Tanaka, K. Hisamatsu, A. Hara
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引用次数: 2

Abstract

Aldehyde dehydrogenase (ALDH) is a ubiquitous intracellular enzyme that catalyzes the irreversible oxidation of a variety of cellular aldehydes. High levels of ALDH activity, involving several isoforms of ALDH (ALDH1A1, ALDH1A2, ALDH1A3 and ALDH8A1), have been proposed as a common feature of stem cells. Adult hematopoietic, neural, and cancer stem cells have been reported to have high ALDH activity, decreased using Aldefluor, a fluorogenic substrate for ALDH. This activity has been attributed to ALDH1A1 expression, an enzyme that has been suggested to regulate stem cell function, including self-protection, differentiation, and expansion of stem cell populations. Recently, it was found that, in the liver, ALDH1A1 was expressed in almost all normal hepatocytes. However, ALDH1A1-overexpressing cells in hepatocellular carcinoma were not co-expressed with putative cancer stem cell markers CD133, CD13, CD90, BMI1, and EpCAM. In this respect, cancer stem cell target therapy related to ALDH1A1 should proceed with some caution; more detailed studies are needed because of this off-target toxicology. However, the subpopulation of cancer stem cells does represent a potential therapeutic target for poor-prognostic, treatment–resistant and recurrent cancer.
醛脱氢酶1A1在干细胞和肿瘤干细胞中的作用
醛脱氢酶(ALDH)是一种普遍存在的细胞内酶,催化多种细胞醛的不可逆氧化。高水平的ALDH活性,包括ALDH的几种亚型(ALDH1A1、ALDH1A2、ALDH1A3和ALDH8A1),被认为是干细胞的共同特征。据报道,成人造血、神经和癌症干细胞具有高ALDH活性,使用aldeflor(一种ALDH的荧光底物)可降低ALDH活性。这种活性归因于ALDH1A1的表达,这种酶被认为可以调节干细胞的功能,包括自我保护、分化和干细胞群体的扩张。最近发现,在肝脏中,ALDH1A1在几乎所有正常肝细胞中都有表达。然而,在肝细胞癌中,aldh1a1过表达的细胞不与假定的癌症干细胞标记物CD133、CD13、CD90、BMI1和EpCAM共表达。在这方面,与ALDH1A1相关的癌症干细胞靶向治疗应该谨慎进行;由于这种脱靶毒理学,需要更详细的研究。然而,癌症干细胞亚群确实代表了预后不良、治疗耐药和复发性癌症的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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